Biomedicines

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23 pages, 4135 KiB

Open AccessArticle

Human Umbilical Cord Mesenchymal Stem Cells Prevent Steroid-Induced Avascular Necrosis of the Femoral Head by Modulating Cellular Autophagy

by Changheng Zhong, Hanzhe Xu, Junwen Chen, Wenxiang Cai, Jianlin Zhou and Hao Peng

Biomedicines 2024, 12(12), 2817; https://doi.org/10.3390/biomedicines12122817 - 12 Dec 2024

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Abstract

Background: Glucocorticoids (GCs) are critical regulatory molecules in the body, commonly utilized in clinical practice for their potent anti-inflammatory and immunosuppressive properties. However, prolonged, high-dose GC therapy is frequently associated with femoral head necrosis, a condition known as glucocorticoid-induced osteonecrosis of the femoral [...] Read more.

Background: Glucocorticoids (GCs) are critical regulatory molecules in the body, commonly utilized in clinical practice for their potent anti-inflammatory and immunosuppressive properties. However, prolonged, high-dose GC therapy is frequently associated with femoral head necrosis, a condition known as glucocorticoid-induced osteonecrosis of the femoral head (GC-ONFH). Emerging evidence suggests that enhanced autophagy may mitigate apoptosis, thereby protecting osteoblasts from GC-induced damage and delaying the progression of ONFH. This study aims to evaluate whether human umbilical cord mesenchymal stem cells (hUCMSCs) can alleviate GC-induced osteoblast injury through autophagy modulation. Methods: In vitro, osteoblasts were exposed to GCs for 48 h, followed by co-culture with hUCMSCs for an additional 12 h before further analysis. The osteoblasts were categorized into four experimental groups: (A) control group, (B) Dex group, (C) Dex + hUCMSC group, and (D) Dex + hUCMSC + 3-MA group. In vivo, rabbits were assigned to one of four groups: Con, MPS, core decompression (CD), and CD + hUCMSC (n = 12 per group), and subsequently subjected to CT imaging and HE staining. Results: In vitro results demonstrate that hUCMSC treatment mitigated GC-induced osteoblast apoptosis and preserved osteogenic activity through autophagy modulation. In vivo, infusion of hUCMSCs enhanced trabecular thickness in the femoral head and improved the femoral head microenvironment. Conclusions: These findings suggest that hUCMSCs protect osteoblasts from GC-induced damage by regulating autophagy, offering new insights into the potential therapeutic use of hUCMSCs for treating ONFH via autophagy enhancement. Full article

(This article belongs to the Special Issue Advanced Research on Muscle and Bone Diseases)

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11 pages, 3525 KiB

Open AccessArticle

The Role of Bone Edema in Plantar Fasciitis Treated with Temperature-Controlled High-Energy Adjustable Multi-Mode Emission Laser (THEAL) and Exercise: A Prospective Randomized Clinical Trial

by Ilaria Covelli, Silvana De Giorgi, Antonio Di Lorenzo, Biagio Moretti, Giuseppe Solarino and Angela Notarnicola

Biomedicines 2024, 12(8), 1729; https://doi.org/10.3390/biomedicines12081729 - 2 Aug 2024

Viewed by 1081

Abstract

Plantar fasciitis is one of the most common causes of foot pain; in 35% of cases, it is also associated with bone edema of the heel. The aim of this study was to investigate the relationship between bone edema and the outcomes of [...] Read more.

Plantar fasciitis is one of the most common causes of foot pain; in 35% of cases, it is also associated with bone edema of the heel. The aim of this study was to investigate the relationship between bone edema and the outcomes of temperature-controlled high-energy adjustable multi-mode emission laser (THEAL) and/or exercises in patients with plantar fasciitis. A prospective randomized clinical trial was designed, in which 48 patients suffering from plantar fasciitis, with or without bone edema, were treated with temperature-controlled high-energy adjustable multi-mode emission laser and exercises (the laser group) or with exercises only (the control group). The patients were evaluated at recruitment (T0) and at 2 (T1) and 6 months (T2), monitoring pain (with the Visual Analogue Scale), functionality (with the Foot Function Index), perception of improvement (with the Roles and Maudsley Score), and fascia thickness (with ultrasound examination). In both groups, there was a significant improvement in pain, functional recovery, perception of remission, and a reduction in plantar fascia thickness at T1 and T2. The laser group presented statistically better values at T2 for the Roles and Maudsley Score (z: 2.21; 0.027). The regression analysis showed that a greater reduction in fascia thickness occurred in the laser group (p-value: 0.047). In conclusion, the two conservative treatments were effective in patients suffering from plantar fasciitis, even in the presence of bone edema, but with lesser results. Full article

(This article belongs to the Special Issue Advanced Research on Muscle and Bone Diseases)

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11 pages, 1284 KiB

Open AccessArticle

Spontaneous Reduction in the Intermetatarsal Angle in Distal First Metatarsal Osteotomies with No Lateral Head Displacement in Hallux Valgus

by Jean-Yves Coillard, Romain Rey, Alessandro Civinini, Fabien Billuart, Eli Schmidt, Cesar de Cesar Netto, Riccardo Sacco and Matthieu Lalevée

Biomedicines 2024, 12(7), 1438; https://doi.org/10.3390/biomedicines12071438 - 27 Jun 2024

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Abstract

Background: The outcomes of first metatarsal (M1) distal osteotomies in hallux valgus (HV) can be improved, especially for intermetatarsal angle (IMA) correction, which is mainly based on lateral displacement of the M1 head (i.e., translation) through the osteotomy. Conversely, there is a spontaneous [...] Read more.

Background: The outcomes of first metatarsal (M1) distal osteotomies in hallux valgus (HV) can be improved, especially for intermetatarsal angle (IMA) correction, which is mainly based on lateral displacement of the M1 head (i.e., translation) through the osteotomy. Conversely, there is a spontaneous reduction in the IMA in first metatarsophalangeal joint (MTP1) arthrodesis. But we do not know whether this can be applied to distal osteotomies. We propose a distal osteotomy, called 3D chevron, which combines supination and varization of the M1 head. This might realign soft tissues around the MTP1, potentially leading to a spontaneous reduction in the IMA by an analogous mechanism to MTP1 fusion. Therefore, our study aimed to assess whether spontaneous reductions in IMAs exist in distal M1 osteotomies in the absence of lateral translations of M1 heads. Methods: A prospective continuous series of 25 3D chevrons was performed. Two groups were formed during surgery. Patients requiring no M1 head lateral displacement were included in the “successful correction without translation” group, and patients requiring M1 head lateral displacement were included in the “failed correction without translation” group. Radiographic analysis was performed preoperatively and at 1 year postoperatively. Results: Twenty-two women and three men, with a mean age of 44.8 ± 14.2 years and a mean body mass index of 22.6 ± 4.1 kg/m², underwent follow-up at one year after surgery. The “successful correction without translation” group was composed of HV with milder deformities (13/25 HVs, median preoperative IMA = 13 (IQR 2)) compared to the “failed correction without translation” group (median IMA = 16 (IQR 2.25) p < 0.001). Spontaneous reductions in IMAs were observed in the “successful correction without translation” group, with a median decrease in the IMA of 6 degrees (CI95%[5.5; 8.0]; p < 0.001) between preoperative and 1-year radiographs. Conclusion: Distal osteotomies allow for spontaneous reduction in the IMA in HV. First metatarsal head translation through an osteotomy should not be considered as the only procedure to correct IMAs in distal osteotomies. Full article

(This article belongs to the Special Issue Advanced Research on Muscle and Bone Diseases)

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10 pages, 4252 KiB

Open AccessArticle

Seroprevalence and Association of Toxoplasma gondii with Bone Health in a Cohort of Osteopenia and Osteoporosis Patients

by Indulekha Karunakaran, Jayagopi Surendar, Pia Ransmann, Marius Brühl, Silvia Kowalski, Victoria Frische, Jamil Hmida, Sabine Nachtsheim, Achim Hoerauf, Dieter C. Wirtz, Marc P. Hübner, Andreas C. Strauss and Frank A. Schildberg

Biomedicines 2024, 12(7), 1400; https://doi.org/10.3390/biomedicines12071400 - 24 Jun 2024

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Abstract

Considering the fact that Toxoplasma is a common parasite of humans and Toxoplasma bradyzoites can reside in skeletal muscle, T. gondii-mediated immune responses may modulate the progression and pathophysiology of another musculoskeletal disorder, osteoporosis. In the current study, we investigated the association [...] Read more.

Considering the fact that Toxoplasma is a common parasite of humans and Toxoplasma bradyzoites can reside in skeletal muscle, T. gondii-mediated immune responses may modulate the progression and pathophysiology of another musculoskeletal disorder, osteoporosis. In the current study, we investigated the association of bone health and Toxoplasma gondii infection status. A total of 138 patients living in Germany with either osteopenia or osteoporosis were included in the study, and they were categorized into two groups, T. gondii uninfected (n = 74) and infected (n = 64), based on the presence of T. gondii-specific IgG antibodies. The demographic and clinical details of the study subjects were collected from the medical records. Logistic regression analysis was performed to delineate the association of bone health parameters with the infection status. The prevalence of toxoplasmosis was 46.4% in the study participants. The infected individuals with osteopenia and osteoporosis showed higher levels of mean spine and femoral T score, Z score, and bone mineral density (BMD), indicating improved bone health compared to the uninfected group. Logistic regression analysis showed that subjects with T. gondii infection displayed increased odds of having a higher mean femur T score, femur BMD, and femur Z score even after adjusting for age, creatinine, and urea levels. However, when the duration of drug intake for osteoporosis was taken into account, the association lost statistical significance. In summary, in this study, an improvement in osteopenia and osteoporosis was observed in Toxoplasma-infected patients, which may be partly due to the longer duration of drug intake for osteoporosis in the infected patient group. Full article

(This article belongs to the Special Issue Advanced Research on Muscle and Bone Diseases)

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13 pages, 1965 KiB

Open AccessArticle

In Vivo Total Ankle Arthroplasty Kinematic Evaluation: A Prospective Radiostereometric Analysis

by Silvio Caravelli, Laura Bragonzoni, Raffaele Zinno, Emanuele Vocale, Erika Pinelli, Giuseppe Barone, Giulio Vara, Stefano Di Paolo, Stefano Zaffagnini and Massimiliano Mosca

Biomedicines 2024, 12(4), 705; https://doi.org/10.3390/biomedicines12040705 - 22 Mar 2024

Cited by 1 | Viewed by 1174

Abstract

Ankle osteoarthritis (OA) represents a significant social burden and is one of the main causes of chronic disability in a rapidly growing part of the world’s population. Total ankle arthroplasty (TAA) has become increasingly popular despite the poor results obtained with the first [...] Read more.

Ankle osteoarthritis (OA) represents a significant social burden and is one of the main causes of chronic disability in a rapidly growing part of the world’s population. Total ankle arthroplasty (TAA) has become increasingly popular despite the poor results obtained with the first dedicated designs. The purpose of this paper was to evaluate the ankle kinematics, in vivo and under weight-bearing conditions, of a TAA through a dynamic model-based radiostereometric analysis (MB-RSA). The clinical evaluation was performed by administering the American Orthopaedic Foot and Ankle Society ankle–hindfoot score and Short Form-36 questionnaires. The kinematic evaluation was conducted through MB-RSA during the execution of an open kinetic chain and a closed kinetic chain motor task. Double radiographic images of the ankle joint were processed using dedicated software to obtain a 3D reconstruction of the ankle prosthetic components’ motion. Eighteen patients (five females) completed the clinical and instrumental preoperative and postoperative evaluations (age 59.1 ± 10.3). All clinical scores showed a marked improvement (p < 0.005). During the closed kinetic chain motor tasks, the ankle showed a total range of motion (ROM) in dorsi-plantarflexion of 19.84°. The parameters in varus–valgus were recorded. Physiological motion can be achieved in TAA, characterized by a wide range of motion and coupling of movements on the three planes. The results of the present work may help to understand the real movement of a widespread TAA model and possibly to improve future designs and instrumentation. Full article

(This article belongs to the Special Issue Advanced Research on Muscle and Bone Diseases)

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23 pages, 6981 KiB

Open AccessArticle

Circular RNA CircFOXO3 Functions as a Competitive Endogenous RNA for Acid-Sensing Ion Channel Subunit 1 Mediating Oxeiptosis in Nucleus Pulposus

by Xi Chen, Ying Song, Guanghui Chen, Baoliang Zhang, Yang Bai, Chuiguo Sun, Dongwei Fan and Zhongqiang Chen

Biomedicines 2024, 12(3), 678; https://doi.org/10.3390/biomedicines12030678 - 18 Mar 2024

Cited by 2 | Viewed by 1417

Abstract

Oxeiptosis is a reactive oxygen species (ROS)-induced pathway of cell death. The involvement of circular RNAs (circRNAs) has been confirmed in the incidence and progression of intervertebral disc degeneration (IVDD). However, whether oxeiptosis occurs in IVDD and how circRNAs regulate oxeiptosis is still [...] Read more.

Oxeiptosis is a reactive oxygen species (ROS)-induced pathway of cell death. The involvement of circular RNAs (circRNAs) has been confirmed in the incidence and progression of intervertebral disc degeneration (IVDD). However, whether oxeiptosis occurs in IVDD and how circRNAs regulate oxeiptosis is still unclear. In this study, we discovered that oxeiptosis could be induced in nucleus pulposus cells (NPCs), and circFOXO3 was significantly upregulated after oxeiptosis induction. Transfection using circFOXO3 small interfering RNA (siRNA) significantly inhibited oxeiptosis in NPCs. Mechanistically, circFOXO3 upregulated acid-sensing ion channel subunit 1 (ASIC1) expression by functioning as a molecular sponge for miR-185-3p and miR-939-5p. Subsequent rescue experiments validated that circFOXO3 could regulate oxeiptosis in NPCs via the miR-185-3p/miR-939-5p-ASIC1 axis. Further research on ASIC1 functions indicated that this regulation was achieved by affecting the Calcium ion (Ca²⁺) influx mediated by ASIC1. A mouse IVDD model was established, and silencing circFOXO3 in vivo was found to inhibit IVDD development and the activation of the oxeiptosis-related pathway. Overall, circFOXO3 is one of the factors contributing to the progression of IVDD by mediating oxeiptosis. Full article

(This article belongs to the Special Issue Advanced Research on Muscle and Bone Diseases)

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15 pages, 1055 KiB

Open AccessArticle

Potential Interaction between WNT16 and Vitamin D on Bone Qualities in Adolescent Idiopathic Scoliosis Patients and Healthy Controls

by Guangpu (Kenneth) Yang, Huanxiong Chen, Ka-Lo Cheng, Man-Fung Tang, Yujia Wang, Lik-Hang (Alec) Hung, Chun-Yiu (Jack) Cheng, King-Lun (Kingston) Mak and Yuk-Wai (Wayne) Lee

Biomedicines 2024, 12(1), 250; https://doi.org/10.3390/biomedicines12010250 - 22 Jan 2024

Viewed by 1956

Abstract

Adolescent idiopathic scoliosis (AIS) is a three-dimensional spinal deformity that is associated with low bone mineral density (BMD). Vitamin D (Vit-D) supplementation has been suggested to improve BMD in AIS, and its outcomes may be related to genetic factors. The present study aimed [...] Read more.

Adolescent idiopathic scoliosis (AIS) is a three-dimensional spinal deformity that is associated with low bone mineral density (BMD). Vitamin D (Vit-D) supplementation has been suggested to improve BMD in AIS, and its outcomes may be related to genetic factors. The present study aimed to (a) investigate the synergistic effect between a low BMD-related gene (wingless-related integration site 16, WNT16) and two important Vit-D pathway genes (Vit-D receptor, VDR, and Vit-D binding protein, VDBP) on serum Vit-D and bone qualities in Chinese AIS patients and healthy adolescents, and (b) to further investigate the effect of ablating Wnt16 on the cortical bone quality and whether diets with different dosages of Vit-D would further influence bone quality during the rapid growth phase in mice in the absence of Wnt16. A total of 519 girls (318 AIS vs. 201 controls) were recruited, and three selected single-nucleotide polymorphisms (SNPs) (WNT16 rs3801387, VDBP rs2282679, and VDR rs2228570) were genotyped. The serum 25(OH)Vit-D level was significantly associated with VDBP rs2282679 alleles (OR = −4.844; 95% CI, −7.521 to −2.167, p < 0.001). Significant multi-locus models were identified by generalized multifactor dimensionality reduction (GMDR) analyses on the serum 25(OH)Vit-D level (p = 0.006) and trabecular area (p = 0.044). In the gene-edited animal study, Wnt16 global knockout (KO) and wildtype (WT) male mice were provided with different Vit-D diets (control chow (1000 IU/Kg) vs. Vit-D-deficient chow (Nil in Vit-D) vs. high-dose Vit-D chow (20,000 IU/Kg)) from 4 weeks to 10 weeks old. Wnt16 global KO mice had significantly lower serum 25(OH)Vit-D levels and higher liver Vdbp mRNA expression levels than WT mice. In addition, Wnt16 global KO mice showed a decrease in bone density, cortical thickness and cortical area compared with WT mice. Interestingly, high-dose Vit-D chow led to lower bone density, cortical thickness, and cortical area in WT mice, which were less obvious in Wnt16 global KO mice. In conclusion, WNT16 may regulate the serum 25(OH)Vit-D level and bone qualities, which might be associated with VDBP expression. Further investigations with a larger sample size and wider spectrum of scoliosis severity are required to validate our findings regarding the interaction between WNT16 and Vit-D status in patients with AIS. Full article

(This article belongs to the Special Issue Advanced Research on Muscle and Bone Diseases)

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10 pages, 687 KiB

Open AccessArticle

How to Generate Self-Efficacy despite Pain: The Role of Catastrophizing and Avoidance in Women with Fibromyalgia

by Patricia Catalá, Lorena Gutiérrez, Carmen Écija and Cecilia Peñacoba

Biomedicines 2024, 12(1), 47; https://doi.org/10.3390/biomedicines12010047 - 24 Dec 2023

Cited by 1 | Viewed by 1433

Abstract

Background and Objective: Fibromyalgia-related pain is influenced by numerous factors, including severity, as well as cognitive profiles based on pain catastrophizing or activity patterns. In this context, self-efficacy is identified as a potential predictor for explaining certain health outcomes. This study aimed to [...] Read more.

Background and Objective: Fibromyalgia-related pain is influenced by numerous factors, including severity, as well as cognitive profiles based on pain catastrophizing or activity patterns. In this context, self-efficacy is identified as a potential predictor for explaining certain health outcomes. This study aimed to contribute to exploring the role of pain avoidance (as activity pattern) between pain severity and self-efficacy along pain catastrophizing. Methods: Through a cross-sectional study, a total of 264 women with fibromyalgia completed self-report measures of pain severity, pain avoidance, pain catastrophizing, and self-efficacy. The severity of the symptoms, the time elapsed since diagnosis, and the time elapsed since the onsets of symptoms were included as covariates to control. Regression-based moderated-mediation analysis was used to test the conditional effect of pain severity on self-efficacy via pain avoidance at varying levels of pain catastrophizing. Results: Pain avoidance mediated the effect of pain severity on self-efficacy. The indirect effects showed a moderated effect when patients scored high on the pain catastrophizing scale. The model evaluated, where catastrophic pain moderates the indirect effect of pain intensity on self-efficacy through pain avoidance, explained 49% of the variance. Conclusions: Catastrophic beliefs associated with pain as being uncontrollable increase the relationship between pain severity and pain avoidance. In turn, pain avoidance is associated with a low perception of capacity. Full article

(This article belongs to the Special Issue Advanced Research on Muscle and Bone Diseases)

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20 pages, 5200 KiB

Open AccessArticle

Interplay between Cultured Human Osteoblastic and Skeletal Muscle Cells: Effects of Conditioned Media on Glucose and Fatty Acid Metabolism

by Ngoc Nguyen Lunde, Nimo Mukhtar Mohamud Osoble, Andrea Dalmao Fernandez, Alfreda S. Antobreh, Abbas Jafari, Sachin Singh, Tuula A. Nyman, Arild C. Rustan, Rigmor Solberg and G. Hege Thoresen

Biomedicines 2023, 11(11), 2908; https://doi.org/10.3390/biomedicines11112908 - 27 Oct 2023

Viewed by 2165

Abstract

The interplay between skeletal muscle and bone is primarily mechanical; however, biochemical crosstalk by secreted mediators has recently gained increased attention. The aim of this study was to investigate metabolic effects of conditioned medium from osteoblasts (OB-CM) on myotubes and vice versa. Human [...] Read more.

The interplay between skeletal muscle and bone is primarily mechanical; however, biochemical crosstalk by secreted mediators has recently gained increased attention. The aim of this study was to investigate metabolic effects of conditioned medium from osteoblasts (OB-CM) on myotubes and vice versa. Human skeletal muscle cells incubated with OB-CM showed increased glucose uptake and oxidation, and mRNA expression of the glucose transporter (GLUT) 1, while fatty acid uptake and oxidation, and mRNA expression of the fatty acid transporter CD36 were decreased. This was supported by proteomic analysis, where expression of proteins involved in glucose uptake, glycolytic pathways, and the TCA cycle were enhanced, and expression of several proteins involved in fatty acid metabolism were reduced. Similar effects on energy metabolism were observed in human bone marrow stromal cells differentiated to osteoblastic cells incubated with conditioned medium from myotubes (SKM-CM), with increased glucose uptake and reduced oleic acid uptake. Proteomic analyses of the two conditioned media revealed many common proteins. Thus, our data may indicate a shift in fuel preference from fatty acid to glucose metabolism in both cell types, induced by conditioned media from the opposite cell type, possibly indicating a more general pattern in communication between these tissues. Full article

(This article belongs to the Special Issue Advanced Research on Muscle and Bone Diseases)

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17 pages, 3125 KiB

Open AccessArticle

Influence of Muscle Mass and Strength on Bone Mineralisation with Consideration of Sclerostin Concentration

by Martyna Patalong-Wójcik, Anna Golara, Katarzyna Zając, Alicja Sokołowska, Mateusz Kozłowski, Aleksandra Tołoczko-Grabarek, Mariola Krzyścin, Agnieszka Brodowska, Agnieszka Janiec, Aleksandra Myszka, Aneta Cymbaluk-Płoska and Elżbieta Sowińska-Przepiera

Biomedicines 2023, 11(6), 1574; https://doi.org/10.3390/biomedicines11061574 - 29 May 2023

Cited by 3 | Viewed by 1649

Abstract

Osteoporosis is a disease characterised by a reduction in bone strength due to increased porosity and impaired mineralisation. In our study, we investigated whether muscle strength and mass exert a significant effect on bone mineral density in young adult women. We also tested [...] Read more.

Osteoporosis is a disease characterised by a reduction in bone strength due to increased porosity and impaired mineralisation. In our study, we investigated whether muscle strength and mass exert a significant effect on bone mineral density in young adult women. We also tested whether sclerostin can be used as an indicator in the assessment of bone mineralisation. The study included 111 patients. All patients had their bone mineral density determined in the L1–L4 section of the lumbar spine and in the whole skeleton. The parameters of fat mass (FM), lean body mass (LBM) and visceral fat mass (VF) were also determined. Metabolic activity of osteocytes was assessed by measuring the serum sclerostin concentration. There was a statistically significant association of both hands’ muscle strength with all parameters expressing bone mineralisation. A statistically significant relationship was also obtained between BMD L1–L4 and the body mass components (FM, LBM). Sclerostin levels in the study did not differ between groups with normal and reduced bone mineral density. Muscle strength assessment may be a potential exponent of reduced bone mineral density, also used clinically in young adult women. The utility of sclerostin in the clinical assessment of bone mineralisation has not been demonstrated. Full article

(This article belongs to the Special Issue Advanced Research on Muscle and Bone Diseases)

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12 pages, 2194 KiB

Open AccessArticle

All-trans Retinoic Acid and Beta-Carotene Increase Sclerostin Production in C2C12 Myotubes

by Franz Ewendt, Anne Lehmann, Maximilian F. Wodak and Gabriele I. Stangl

Biomedicines 2023, 11(5), 1432; https://doi.org/10.3390/biomedicines11051432 - 12 May 2023

Cited by 1 | Viewed by 1955

Abstract

Sclerostin is a protein secreted by osteocytes whose encoding gene SOST is regulated by mechanical stimuli, cytokines, and all-trans retinoic acid (ATRA) and mediates antianabolic effects on bone formation as an inhibitor of the canonical Wnt/β-catenin pathway. Interestingly, skeletal muscle has recently [...] Read more.

Sclerostin is a protein secreted by osteocytes whose encoding gene SOST is regulated by mechanical stimuli, cytokines, and all-trans retinoic acid (ATRA) and mediates antianabolic effects on bone formation as an inhibitor of the canonical Wnt/β-catenin pathway. Interestingly, skeletal muscle has recently been identified as another source of sclerostin, suggesting that the musculature may play an important role in maintaining bone mass. However, regulators of muscular SOST expression are virtually unknown. This study investigates the influence of ATRA and the provitamin A derivative beta-carotene (β-C) on sclerostin synthesis in muscle cells. The impact of ATRA, its synthetic analog TTNPB, and β-C on Sost transcription was analyzed by qRT-PCR in C2C12 myotubes and the secreted sclerostin protein by ELISA. ATRA strongly increases the sclerostin synthesis in C2C12 myotubes in a dose-dependent manner. The stimulating effect of ATRA and TTNPB on Sost is largely reduced in the presence of the retinoic acid receptor inhibitor AGN193109. β-C also increases the Sost expression, but this effect vanishes when β-C is coincubated with beta-carotene 15,15′-monooxygenase 1 (BCMO1)-specific siRNA. Thus, ATRA is a potent stimulator of sclerostin release in muscle cells. β-C can also increase Sost mRNA abundance, but this effect depends on the conversion to a retinoid. Full article

(This article belongs to the Special Issue Advanced Research on Muscle and Bone Diseases)

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14 pages, 450 KiB

Open AccessArticle

COVID-19 in Older Patients: Assessment of Post-COVID-19 Sarcopenia

by Almudena López-Sampalo, Lidia Cobos-Palacios, Alberto Vilches-Pérez, Jaime Sanz-Cánovas, Antonio Vargas-Candela, Juan José Mancebo-Sevilla, Halbert Hernández-Negrín, Ricardo Gómez-Huelgas and María Rosa Bernal-López

Biomedicines 2023, 11(3), 733; https://doi.org/10.3390/biomedicines11030733 - 28 Feb 2023

Cited by 5 | Viewed by 2360

Abstract

(1) Background: Acute COVID-19 infections produce alterations in the skeletal muscle, leading to acute sarcopenia, but the medium- and long-term consequences are still unknown. The aim of this study was to evaluate: (1) body composition; (2) muscle strength and the prevalence of sarcopenia; [...] Read more.

(1) Background: Acute COVID-19 infections produce alterations in the skeletal muscle, leading to acute sarcopenia, but the medium- and long-term consequences are still unknown. The aim of this study was to evaluate: (1) body composition; (2) muscle strength and the prevalence of sarcopenia; and (3) the relationship between muscle strength with symptomatic and functional evolution in older patients affected by/recovered from COVID-19; (2) Methods: A prospective, longitudinal study of patients aged ≥65 years who had suffered from COVID-19 infection between 1 March and 31 May 2020, as confirmed by PCR or subsequent seroconversion. Persistent symptoms, as well as anthropometric, clinical, and analytical characteristics, were analyzed at 3 and 12 months after infection. The degree of sarcopenia was determined by dynamometry and with SARC-F; (3) Results: 106 participants, aged 76.8 ± 7 years, were included. At 3 months postinfection, a high percentage of sarcopenic patients was found, especially among women and in those with hospitalization. At 12 months postinfection, this percentage had decreased, coinciding with a functional and symptomatic recovery, and the normalization of inflammatory parameters, especially interleukin-6 (4.7 ± 11.6 pg/mL vs. 1.5 ± 2.4 pg/mL, p < 0.05). The improvement in muscle strength was accompanied by significant weight gain (71.9 ± 12.1 kg vs. 74.7 ± 12.7 kg, p < 0.001), but not by an increase in lean mass (49.6 ± 10 vs. 49.9 ± 10, p 0.29); (4) Conclusions: Older COVID-19 survivors presented a functional, clinical, and muscular recovery 12 months postinfection. Even so, it is necessary to carry out comprehensive follow-ups and assessments that include aspects of nutrition and physical activity. Full article

(This article belongs to the Special Issue Advanced Research on Muscle and Bone Diseases)

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Review

Jump to: Research, Other

16 pages, 1053 KiB

Open AccessReview

MicroRNAs as Biomarkers in Spinal Muscular Atrophy

by Maruša Barbo, Damjan Glavač, Gregor Jezernik and Metka Ravnik-Glavač

Biomedicines 2024, 12(11), 2428; https://doi.org/10.3390/biomedicines12112428 - 23 Oct 2024

Viewed by 948

Abstract

Spinal muscular atrophy (SMA) is a severe neurodegenerative disease caused by the loss of the survival motor neuron (SMN) protein, leading to degeneration of anterior motor neurons and resulting in progressive muscle weakness and atrophy. Given that SMA has a single, well-defined genetic [...] Read more.

Spinal muscular atrophy (SMA) is a severe neurodegenerative disease caused by the loss of the survival motor neuron (SMN) protein, leading to degeneration of anterior motor neurons and resulting in progressive muscle weakness and atrophy. Given that SMA has a single, well-defined genetic cause, gene-targeted therapies have been developed, aiming to increase SMN production in SMA patients. The SMN protein is likely involved in the synthesis of microRNAs (miRNAs), and dysregulated miRNA expression is increasingly associated with the pathophysiology of SMA. Currently, there is a lack of reliable biomarkers to monitor SMA; therefore, the search for novel SMA biomarkers, including miRNAs, is crucial as reliable tools are needed to track disease progression, predict the response to therapy and understand the different clinical outcomes of available treatments. In this review, we compile data on miRNAs associated with SMA pathogenesis and their potential use as biomarkers. Based on current knowledge, the most frequently deregulated miRNAs between SMA patients and controls, as well as pre- and post-treatment in SMA patients, include miR-1-3p, miR-133a-3p, miR-133b, and miR-206. These findings offer promising possibilities for improving patient classification and monitoring disease progression and response to treatment. Additionally, these findings provide insights into the broader molecular mechanisms and networks of SMA that could inform the development of future therapeutic strategies. Full article

(This article belongs to the Special Issue Advanced Research on Muscle and Bone Diseases)

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12 pages, 969 KiB

Open AccessReview

The Pathogenetic Role of RANK/RANKL/OPG Signaling in Osteoarthritis and Related Targeted Therapies

by Gabriele Di Cicco, Emanuela Marzano, Andrea Mastrostefano, Dario Pitocco, Rodrigo Simões Castilho, Roberto Zambelli, Antonio Mascio, Tommaso Greco, Virginia Cinelli, Chiara Comisi, Giulio Maccauro and Carlo Perisano

Biomedicines 2024, 12(10), 2292; https://doi.org/10.3390/biomedicines12102292 - 10 Oct 2024

Viewed by 1546

Abstract

Background: Osteoarthritis (OA) is the most common degenerative joint disease and affects millions of people worldwide, particularly the elderly population. The pathophysiology of OA is complex and involves multiple factors. Methods: Several studies have emphasized the crucial role of inflammation in this process. [...] Read more.

Background: Osteoarthritis (OA) is the most common degenerative joint disease and affects millions of people worldwide, particularly the elderly population. The pathophysiology of OA is complex and involves multiple factors. Methods: Several studies have emphasized the crucial role of inflammation in this process. The receptor activator of NF-κB ligand (RANKL), the receptor activator of NF-κB (RANK), and osteoprotegerin (OPG) trigger a signaling cascade that leads to the excessive production of RANKL in the serum. Conclusions: The aim of this narrative review is (i) to assess the role of the RANK/RANKL/OPG signaling pathway in the context of OA progression, focusing especially on the physiopathology and on all the mechanisms leading to the activation of the inflammatory cascade, and (ii) to evaluate all the potential therapeutic strategies currently available that restore balance to bone formation and resorption, reducing structural abnormalities and relieving pain in patients with OA. Full article

(This article belongs to the Special Issue Advanced Research on Muscle and Bone Diseases)

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22 pages, 7031 KiB

Open AccessReview

Investigating and Practicing Orthopedics at the Intersection of Sex and Gender: Understanding the Physiological Basis, Pathology, and Treatment Response of Orthopedic Conditions by Adopting a Gender Lens: A Narrative Overview

by Carlo Biz, Rola Khamisy-Farah, Luca Puce, Lukasz Szarpak, Manlio Converti, Halil İbrahim Ceylan, Alberto Crimì, Nicola Luigi Bragazzi and Pietro Ruggieri

Biomedicines 2024, 12(5), 974; https://doi.org/10.3390/biomedicines12050974 - 29 Apr 2024

Cited by 5 | Viewed by 2325

Abstract

In the biomedical field, the differentiation between sex and gender is crucial for enhancing the understanding of human health and personalizing medical treatments, particularly within the domain of orthopedics. This distinction, often overlooked or misunderstood, is vital for dissecting and treating musculoskeletal conditions [...] Read more.

In the biomedical field, the differentiation between sex and gender is crucial for enhancing the understanding of human health and personalizing medical treatments, particularly within the domain of orthopedics. This distinction, often overlooked or misunderstood, is vital for dissecting and treating musculoskeletal conditions effectively. This review delves into the sex- and gender-specific physiology of bones, cartilage, ligaments, and tendons, highlighting how hormonal differences impact the musculoskeletal system’s structure and function, and exploring the physiopathology of orthopedic conditions from an epidemiological, molecular, and clinical perspective, shedding light on the discrepancies in disease manifestation across sexes. Examples such as the higher rates of deformities (adolescent idiopathic and adult degenerative scoliosis and hallux valgus) in females and osteoporosis in postmenopausal women illustrate the critical role of sex and gender in orthopedic health. Additionally, the review addresses the morbidity–mortality paradox, where women, despite appearing less healthy on frailty indexes, show lower mortality rates, highlighting the complex interplay between biological and social determinants of health. Injuries and chronic orthopedic conditions such osteoarthritis exhibit gender- and sex-specific prevalence and progression patterns, necessitating a nuanced approach to treatment that considers these differences to optimize outcomes. Moreover, the review underscores the importance of recognizing the unique needs of sexual minority and gender-diverse individuals in orthopedic care, emphasizing the impact of gender-affirming hormone therapy on aspects like bone health and perioperative risks. To foster advancements in sex- and gender-specific orthopedics, we advocate for the strategic disaggregation of data by sex and gender and the inclusion of “Sexual Orientation and Gender Identity” (SOGI) data in research and clinical practice. Such measures can enrich clinical insights, ensure tailored patient care, and promote inclusivity within orthopedic treatments, ultimately enhancing the precision and effectiveness of care for diverse patient populations. Integrating sex and gender considerations into orthopedic research and practice is paramount for addressing the complex and varied needs of patients. By embracing this comprehensive approach, orthopedic medicine can move towards more personalized, effective, and inclusive treatment strategies, thereby improving patient outcomes and advancing the field. Full article

(This article belongs to the Special Issue Advanced Research on Muscle and Bone Diseases)

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22 pages, 867 KiB

Open AccessReview

The Use of Extracellular Vesicles in Achilles Tendon Repair: A Systematic Review

by Varun Kasula, Vikram Padala, Nithin Gupta, David Doyle, Kian Bagheri, Albert Anastasio and Samuel Bruce Adams

Biomedicines 2024, 12(5), 942; https://doi.org/10.3390/biomedicines12050942 - 23 Apr 2024

Cited by 1 | Viewed by 1945

Abstract

Achilles tendon (AT) pathologies are common musculoskeletal conditions that can significantly impair function. Despite various traditional treatments, recovery is often slow and may not restore full functionality. The use of extracellular vesicles (EVs) has emerged as a promising therapeutic option due to their [...] Read more.

Achilles tendon (AT) pathologies are common musculoskeletal conditions that can significantly impair function. Despite various traditional treatments, recovery is often slow and may not restore full functionality. The use of extracellular vesicles (EVs) has emerged as a promising therapeutic option due to their role in cell signaling and tissue regeneration. This systematic review aims to consolidate current in vivo animal study findings on the therapeutic effects of EVs on AT injuries. An extensive literature search was conducted using the PubMed, Scopus, and Embase databases for in vivo animal studies examining the effects of EVs on AT pathologies. The extracted variables included but were not limited to the study design, type of EVs used, administration methods, efficacy of treatment, and proposed therapeutic mechanisms. After screening, 18 studies comprising 800 subjects were included. All but one study reported that EVs augmented wound healing processes in the AT. The most proposed mechanisms through which this occurred were gene regulation of the extracellular matrix (ECM), the enhancement of macrophage polarization, and the delivery of therapeutic microRNAs to the injury site. Further research is warranted to not only explore the therapeutic potential of EVs in the context of AT pathologies, but also to establish protocols for their clinical application. Full article

(This article belongs to the Special Issue Advanced Research on Muscle and Bone Diseases)

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17 pages, 1684 KiB

Open AccessReview

Cellular and Molecular Mechanisms of Heterotopic Ossification in Fibrodysplasia Ossificans Progressiva

by Loreilys Mejias Rivera, Eileen M. Shore and Foteini Mourkioti

Biomedicines 2024, 12(4), 779; https://doi.org/10.3390/biomedicines12040779 - 2 Apr 2024

Cited by 6 | Viewed by 2423

Abstract

Fibrodysplasia ossificans progressiva (FOP) is a debilitating genetic disorder characterized by recurrent episodes of heterotopic ossification (HO) formation in muscles, tendons, and ligaments. FOP is caused by a missense mutation in the ACVR1 gene (activin A receptor type I), an important signaling receptor [...] Read more.

Fibrodysplasia ossificans progressiva (FOP) is a debilitating genetic disorder characterized by recurrent episodes of heterotopic ossification (HO) formation in muscles, tendons, and ligaments. FOP is caused by a missense mutation in the ACVR1 gene (activin A receptor type I), an important signaling receptor involved in endochondral ossification. The ACVR1^R206^H mutation induces increased downstream canonical SMAD-signaling and drives tissue-resident progenitor cells with osteogenic potential to participate in endochondral HO formation. In this article, we review aberrant ACVR1^R206H signaling and the cells that give rise to HO in FOP. FOP mouse models and lineage tracing analyses have been used to provide strong evidence for tissue-resident mesenchymal cells as cellular contributors to HO. We assess how the underlying mutation in FOP disrupts muscle-specific dynamics during homeostasis and repair, with a focus on muscle-resident mesenchymal cells known as fibro-adipogenic progenitors (FAPs). Accumulating research points to FAPs as a prominent HO progenitor population, with ACVR1^R206^H FAPs not only aberrantly differentiating into chondro-osteogenic lineages but creating a permissive environment for bone formation at the expense of muscle regeneration. We will further discuss the emerging role of ACVR1^R206^H FAPs in muscle regeneration and therapeutic targeting of these cells to reduce HO formation in FOP. Full article

(This article belongs to the Special Issue Advanced Research on Muscle and Bone Diseases)

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15 pages, 842 KiB

Open AccessReview

Peak Bone Mass Formation: Modern View of the Problem

by Karina Akhiiarova, Rita Khusainova, Ildar Minniakhmetov, Natalia Mokrysheva and Anton Tyurin

Biomedicines 2023, 11(11), 2982; https://doi.org/10.3390/biomedicines11112982 - 6 Nov 2023

Cited by 3 | Viewed by 2671

Abstract

Peak bone mass is the amount of bone tissue that is formed when a stable skeletal state is achieved at a young age. To date, there are no established peak bone mass standards nor clear data on the age at which peak bone [...] Read more.

Peak bone mass is the amount of bone tissue that is formed when a stable skeletal state is achieved at a young age. To date, there are no established peak bone mass standards nor clear data on the age at which peak bone mass occurs. At the same time, the level of peak bone mass at a young age is an important predictor of the onset of primary osteoporosis. The purpose of this review is to analyze the results of studies of levels of peak bone mass in general, the age of its onset, as well as factors influencing its formation. Factors such as hormonal levels, body composition, physical activity, nutrition, heredity, smoking, lifestyle, prenatal predictors, intestinal microbiota, and vitamin and micronutrient status were considered, and a comprehensive scheme of the influence of these factors on the level of peak bone mass was created. Determining the standards and timing of the formation of peak bone mass, and the factors affecting it, will help in the development of measures to prevent its shortage and the consequent prevention of osteoporosis and concomitant diseases. Full article

(This article belongs to the Special Issue Advanced Research on Muscle and Bone Diseases)

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14 pages, 5909 KiB

Open AccessReview

Imaging Plays a Key Role in the Diagnosis and Control of the Treatment of Bone Sarcoidosis

by Katarzyna Błasińska, Małgorzata Ewa Jędrych, Lucyna Opoka, Witold Tomkowski and Monika Szturmowicz

Biomedicines 2023, 11(7), 1866; https://doi.org/10.3390/biomedicines11071866 - 30 Jun 2023

Cited by 2 | Viewed by 1979

Abstract

Sarcoidosis is a multisystem granulomatous disease of unknown origin. The most frequent localizations are thoracic lymph nodes and/or parenchymal lung disease, nevertheless any other organ may be involved. Musculoskeletal sarcoidosis, previously considered a rare manifestation of the disease, is presently recognized with increasing [...] Read more.

Sarcoidosis is a multisystem granulomatous disease of unknown origin. The most frequent localizations are thoracic lymph nodes and/or parenchymal lung disease, nevertheless any other organ may be involved. Musculoskeletal sarcoidosis, previously considered a rare manifestation of the disease, is presently recognized with increasing frequency, due to the development of modern imaging modalities. The classical X-ray sign of bone sarcoidosis is the image of lace in the phalanges of the hands. Most other locations present with atypical radiological images. Therefore, they may mimic metastatic neoplastic disease, especially when they are the first sign of sarcoidosis not previously recognized. On such occasions, none of the imaging methods will give the correct diagnosis, histopathological verification, monitoring of lesions or clinical data in a patient with confirmed sarcoidosis are indicated. The article summarizes the current status of knowledge concerning the recognition and therapy of bone sarcoidosis. In addition, an illustrative case of patient with bone and bone marrow sarcoidosis is presented. Full article

(This article belongs to the Special Issue Advanced Research on Muscle and Bone Diseases)

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15 pages, 4021 KiB

Open AccessSystematic Review

Efficacy of Bisphosphonates in Total Hip Arthroplasty Patients: Systematic Review and Meta-Analysis

by Alberto Di Martino, Konstantinos Valtetsiotis, Valentino Rossomando, Matteo Brunello, Barbara Bordini, Claudio D’Agostino, Federico Ruta, Francesco Traina and Cesare Faldini

Biomedicines 2024, 12(8), 1778; https://doi.org/10.3390/biomedicines12081778 - 6 Aug 2024

Viewed by 692

Abstract

The scientific literature suggests that, if periprosthetic osteolysis (PPO) is not treated, it may have a negative impact on the results of a total hip replacement and possibly result in failure. This systematic review aimed to determine the efficacy of using bisphosphonates preventatively [...] Read more.

The scientific literature suggests that, if periprosthetic osteolysis (PPO) is not treated, it may have a negative impact on the results of a total hip replacement and possibly result in failure. This systematic review aimed to determine the efficacy of using bisphosphonates preventatively to limit PPO after a total hip arthroplasty (THA). Methods: A systematic review and meta-analysis were conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A PICOS template was developed to ensure a structured approach. A search for relevant studies was performed across four databases, including Pubmed, Scopus, Embase, and Cochrane. They were all last searched on March 1st and were assessed using the Cochrane risk of bias tool for randomised studies. Results: The final analysis included seven studies with a total of 126 study group participants and 144 control group participants. The studies looked at Bony Mass Density in terms of bone loss on Gruen’s femoral zones after THA in a bisphosphonate (treatment) and control group (placebo/no treatment). The analysis revealed a statistically significant difference (p < 0.05) in favour of the bisphosphonate group in many of the included studies at 6, 12, and 24 postoperative months. Conclusions: This systematic review and meta-analysis, using the most recent applicable studies, showed the efficacy of bisphosphonates in limiting periprosthetic osteolysis after THA in a period between 6 and 24 postoperative months. Future studies should focus increasing group sizes and collecting results beyond the 2-year mark. Full article

(This article belongs to the Special Issue Advanced Research on Muscle and Bone Diseases)

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