Musculoskeletal Diseases: From Molecular Basis to Therapy

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cell Biology and Pathology".

Deadline for manuscript submissions: closed (31 March 2023) | Viewed by 46851

Special Issue Editors


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Guest Editor
1 Musculoskeletal Pathology and Oncology Laboratory, Department of Surgery, Oncology and Gastroenterology (DISCOG), University of Padova, 35129 Padova, Italy
2 Orthopedics and Orthopedic Oncology, Department of Surgery, Oncology and Gastroenterology (DiSCOG), University of Padova, 35129 Padova, Italy
Interests: inflammation; molecular biology; cell biology; osteoarthritis; cartilage; musculoskeletal diseases; bone cancer; synovium; infrapatellar fat pad; chodrosarcoma
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
1. Musculoskeletal Pathology and Oncology Laboratory, Orthopaedic and Traumatologic Clinic, Department of Surgery, Oncology and Gastroenterology (DISCOG), University of Padova, 35128 Padova, Italy
2. Orthopedics and Orthopedic Oncology, Department of Surgery, Oncology and Gastroenterology (DiSCOG), University-Hospital of Padova, 35128 Padova, Italy
Interests: musculoskeletal diseases; bone cancer; chondrosarcoma; osteoarthritis; inflammation; Joint tissues; aging; molecular biology; cell biology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Musculoskeletal diseases comprise numerous different disorders (more than 150 conditions) affecting the locomotor system (joints, bones, muscles, cartilage, meniscus and tendon tissues) and are associated with significant morbidity and disability. A recent analysis of the Global Burden of Disease estimated that approximately 1.71 billion people globally have musculoskeletal conditions. The number of affected individuals is expected to grow as the population ages. Thus, a better understanding of the etiology and new and more effective therapeutic treatments are needed. The purpose of this Special Issue is to report advances in pathophysiological mechanisms, predictive biomarkers and preclinical therapeutic approaches to musculoskeletal disorders, with a particular focus on bone cancers and osteoarthritis.

Authors are invited to contribute to this Special Issue with original research articles and comprehensive reviews.

Topics include, but are not limited to, the following:

  • Pathophysiological studies related to musculoskeletal diseases;
  • Molecular, biochemical and biomechanical mechanisms involved in the etiology and progression of musculoskeletal disorders;
  • Identification of biomarkers useful for early diagnosis and/or predictive of prognosis;
  • Preclinical research of potential drugs and cell-based strategies for the treatment of musculoskeletal disorders.

Dr. Elisa Belluzzi
Dr. Assunta Pozzuoli
Guest Editors

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Keywords

  • musculoskeletal diseases
  • bone cancer
  • soft tissue cancer
  • bone metastasis
  • natural compounds
  • anticancer drugs
  • osteoarthritis
  • joint tissues
  • biomarkers
  • inflammation
  • microRNAs
  • exosomes

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Published Papers (15 papers)

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Editorial

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6 pages, 212 KiB  
Editorial
Musculoskeletal Diseases: From Molecular Basis to Therapy
by Elisa Belluzzi, Assunta Pozzuoli and Pietro Ruggieri
Biomedicines 2024, 12(1), 32; https://doi.org/10.3390/biomedicines12010032 - 22 Dec 2023
Viewed by 1705
Abstract
Musculoskeletal diseases (MSDs) comprise a plethora of different disorders (more than 150 conditions) affecting the locomotor system [...] Full article
(This article belongs to the Special Issue Musculoskeletal Diseases: From Molecular Basis to Therapy)

Research

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20 pages, 7361 KiB  
Article
Medical Prospect of Melatonin in the Intervertebral Disc Degeneration through Inhibiting M1-Type Macrophage Polarization via SIRT1/Notch Signaling Pathway
by Xinyu Dou, Qipeng Luo, Linzhen Xie, Xuchang Zhou, Chunyu Song, Meijuan Liu, Xiao Liu, Yunlong Ma and Xiaoguang Liu
Biomedicines 2023, 11(6), 1615; https://doi.org/10.3390/biomedicines11061615 - 1 Jun 2023
Cited by 7 | Viewed by 2184
Abstract
The study aims to explore the medical prospect of melatonin (MLT) and the underlying therapeutic mechanism of MLT-mediated macrophage (Mφ) polarization on the function of nucleus pulposus (NP) in intervertebral disc degeneration (IDD). RAW 264.7 Mφs were induced by lipopolysaccharide (LPS) to simulate [...] Read more.
The study aims to explore the medical prospect of melatonin (MLT) and the underlying therapeutic mechanism of MLT-mediated macrophage (Mφ) polarization on the function of nucleus pulposus (NP) in intervertebral disc degeneration (IDD). RAW 264.7 Mφs were induced by lipopolysaccharide (LPS) to simulate Mφ polarization and the inflammatory reaction of Mφs with or without MLT were detected. Conditioned medium (CM) collected from these activated Mφs with or without MLT treatment were further used to incubate NP cells. The oxidative stress, inflammation and extracellular matrix (ECM) metabolism in NP cells were determined. Then, the changes in SIRT1/Notch signaling were detected. The agonist (SRT1720) and inhibitor (EX527) of SIRT1 were used to further explore the association among MLT. The interaction between SIRT1 and NICD was detected by immunoprecipitation (IP). Finally, puncture-induced rat IDD models were established and IDD degrees were clarified by X-ray, MRI, H&E staining and immunofluorescence (IF). The results of flow cytometry and inflammation detection indicated that LPS could induce M1-type Mφ polarization with pro-inflammatory properties. MLT significantly inhibited the aforementioned process and inhibited M1-type Mφ polarization, accompanied by the alleviation of inflammation. Compared with those without MLT, the levels of oxidative stress, pro-inflammatory cytokines and ECM catabolism in NP cells exposed to CM with MLT were markedly downregulated in a dose-dependent manner. The inhibition of SIRT1 and the enhancement of Notch were observed in activated Mφs and they can be reversed after MLT treatment. This prediction was further confirmed by using the SRT1720 and EX527 to activate or inhibit the signaling. The interaction between SIRT1 and NICD was verified by IP. In vivo study, the results of MRI, Pfirrmann grade scores and H&E staining demonstrated the degree of disc degeneration was significantly lower in the MLT-treated groups when compared with the IDD control group. The IF data showed M1-type Mφ polarization decreased after MLT treatment. MLT could inhibit M1-type Mφ polarization and ameliorate the NP cell injury caused by inflammation in vitro and vivo, which is of great significance for the remission of IDD. The SIRT1/Notch signaling pathway is a promising target for MLT to mediate Mφ polarization. Full article
(This article belongs to the Special Issue Musculoskeletal Diseases: From Molecular Basis to Therapy)
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14 pages, 2404 KiB  
Article
Effects on Bone and Muscle upon Treadmill Interval Training in Hypogonadal Male Rats
by Ioannis Stratos, Ingmar Rinas, Konrad Schröpfer, Katharina Hink, Philipp Herlyn, Mario Bäumler, Tina Histing, Sven Bruhn, Brigitte Müller-Hilke, Michael D. Menger, Brigitte Vollmar and Thomas Mittlmeier
Biomedicines 2023, 11(5), 1370; https://doi.org/10.3390/biomedicines11051370 - 5 May 2023
Cited by 3 | Viewed by 1886
Abstract
Testosterone deficiency in males is linked to various pathological conditions, including muscle and bone loss. This study evaluated the potential of different training modalities to counteract these losses in hypogonadal male rats. A total of 54 male Wistar rats underwent either castration (ORX, [...] Read more.
Testosterone deficiency in males is linked to various pathological conditions, including muscle and bone loss. This study evaluated the potential of different training modalities to counteract these losses in hypogonadal male rats. A total of 54 male Wistar rats underwent either castration (ORX, n = 18) or sham castration (n = 18), with 18 castrated rats engaging in uphill, level, or downhill interval treadmill training. Analyses were conducted at 4, 8, and 12 weeks postsurgery. Muscle force of the soleus muscle, muscle tissue samples, and bone characteristics were analyzed. No significant differences were observed in cortical bone characteristics. Castrated rats experienced decreased trabecular bone mineral density compared to sham-operated rats. However, 12 weeks of training increased trabecular bone mineral density, with no significant differences among groups. Muscle force measurements revealed decreased tetanic force in castrated rats at week 12, while uphill and downhill interval training restored force to sham group levels and led to muscle hypertrophy compared to ORX animals. Linear regression analyses showed a positive correlation between bone biomechanical characteristics and muscle force. The findings suggest that running exercise can prevent bone loss in osteoporosis, with similar bone restoration effects observed across different training modalities. Full article
(This article belongs to the Special Issue Musculoskeletal Diseases: From Molecular Basis to Therapy)
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14 pages, 2425 KiB  
Article
In Vitro Effects of PTH (1-84) on Human Skeletal Muscle-Derived Satellite Cells
by Cecilia Romagnoli, Roberto Zonefrati, Elena Lucattelli, Marco Innocenti, Roberto Civinini, Teresa Iantomasi and Maria Luisa Brandi
Biomedicines 2023, 11(4), 1017; https://doi.org/10.3390/biomedicines11041017 - 27 Mar 2023
Cited by 4 | Viewed by 1822
Abstract
Parathyroid hormone (PTH) is a hormone secreted by the parathyroid glands. Despite its well-known characterized anabolic and catabolic actions on the skeleton, the in vitro effects of PTH on skeletal muscle cells are limited and generally performed on animal models. The aim of [...] Read more.
Parathyroid hormone (PTH) is a hormone secreted by the parathyroid glands. Despite its well-known characterized anabolic and catabolic actions on the skeleton, the in vitro effects of PTH on skeletal muscle cells are limited and generally performed on animal models. The aim of this study was to evaluate the effects of a short impulse of PTH (1-84) on the proliferation and the differentiation of skeletal muscle satellite cells isolated from human biopsies. The cells were exposed for 30 min to different concentrations of PTH (1-84), from 10−6 mol/L to 10−12 mol/L. ELISA was used to assay cAMP and the myosin heavy-chain (MHC) protein. The proliferation was assayed by BrdU and the differentiation by RealTime-qPCR. A statistical analysis was performed by ANOVA followed by Bonferroni’s test. No significant variations in cAMP and the proliferation were detected in the isolated cells treated with PTH. On the other hand, 10−7 mol/L PTH on differentiated myotubes has shown significant increases in cAMP (p ≤ 0.05), in the expression of myogenic differentiation genes (p ≤ 0.001), and in the MHC protein (p ≤ 0.01) vs. untreated controls. This work demonstrates for the first time the in vitro effects of PTH (1-84) on human skeletal muscle cells and it opens new fields of investigation in muscle pathophysiology. Full article
(This article belongs to the Special Issue Musculoskeletal Diseases: From Molecular Basis to Therapy)
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12 pages, 1925 KiB  
Article
Brain-Type Creatine Kinase Release from Cultured Osteoclasts Exposed to Neridronate in Children Affected by Osteogenesis Imperfecta Type 1
by Maria Felicia Faienza, Albina Tummolo, Mauro Celli, Roberto Finocchiaro, Laura Piacente, Francesca Di Serio, Grazia Paola Nicchia, Giacomina Brunetti and Patrizia D’Eufemia
Biomedicines 2023, 11(2), 458; https://doi.org/10.3390/biomedicines11020458 - 4 Feb 2023
Cited by 2 | Viewed by 1660
Abstract
Brain-type creatine kinase (CK-BB) increases during osteoclastogenesis, with high circulating amounts in type I osteogenesis imperfecta (OI) following treatment with neridronate, a bisphosphonate able to inhibit osteoclast activity and survival. The aim of this study was to demonstrate the correlation between osteoclastogenesis and [...] Read more.
Brain-type creatine kinase (CK-BB) increases during osteoclastogenesis, with high circulating amounts in type I osteogenesis imperfecta (OI) following treatment with neridronate, a bisphosphonate able to inhibit osteoclast activity and survival. The aim of this study was to demonstrate the correlation between osteoclastogenesis and CK-BB release from OI patients’ osteoclasts treated with different concentrations of neridronate. Our patients showed reduced bone quality, increased levels of CTX I, a marker of bone resorption, and decreased levels of OPG, an inhibitor of osteoclastogenesis. In OI patients, the presence of MCSF and RANKL determined an increased secretion of CK-BB from osteoclasts (p = 0.04) compared with control conditions without these cytokines; interestingly, in the absence of these factors, the secretion of CK-BB is significantly elevated at 3 µmol/L compared with 0.03 and 1 µmol/L (p = 0.007). In healthy donors’ cultures, the higher concentration of CK-BB can be detected following stimulation with 3 µmol/L neridronate compared with the untreated condition both with and without MCSF and RANKL (p = 0.03 and p = 0.006, respectively). Consistently, in osteoclast cultures, neridronate treatment is associated with a decrease in multinucleated TRAP+ cells, together with morphology changes typical of apoptosis. Consistently, in the media of the same osteoclast cultures, we demonstrated a significant increase in caspase-3 levels. In conclusion, our findings support the idea that CK-BB levels increase in the serum of OI-treated patients. Full article
(This article belongs to the Special Issue Musculoskeletal Diseases: From Molecular Basis to Therapy)
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22 pages, 12967 KiB  
Article
Fibrosis-Associated Signaling Molecules Are Differentially Expressed in Palmar Connective Tissues of Patients with Carpal Tunnel Syndrome and Dupuytren’s Disease
by Ivo Tripković, Marin Ogorevc, Dubravka Vuković, Mirna Saraga-Babić and Snježana Mardešić
Biomedicines 2022, 10(12), 3214; https://doi.org/10.3390/biomedicines10123214 - 11 Dec 2022
Cited by 3 | Viewed by 2211
Abstract
Carpal tunnel syndrome (CTS) and Dupuytren’s disease (DD) are fibrotic conditions that affect the connective tissue of the hand and limit its functionality. The exact molecular mechanism underlying the fibrosis is unknown, and only some profibrotic factors have been investigated. In this cross-sectional [...] Read more.
Carpal tunnel syndrome (CTS) and Dupuytren’s disease (DD) are fibrotic conditions that affect the connective tissue of the hand and limit its functionality. The exact molecular mechanism underlying the fibrosis is unknown, and only some profibrotic factors have been investigated. In this cross-sectional study, we analyzed the expression of FGF signaling pathway molecules associated with fibrotic changes in the palmar fascia and the flexor retinaculum of 15 CTS patients and both clinically affected and unaffected palmar fascia of 15 DD patients, using immunofluorescence techniques. The expression of FGFR1, FGFR2, and CTGF in the blood vessel walls and surrounding connective tissue cells differed significantly between the analyzed groups, with changes in expression present even in clinically unremarkable tissues from DD patients. We also found altered expression of the analyzed factors, as well as TGF-β1 and syndecan-1 in DD-associated sweat glands, possibly implicating their role in the pathophysiology of the disease. The increased expression of profibrotic factors in the clinically unaffected palmar fascia of DD patients may indicate that more extensive excision is needed during surgical treatment, while the profibrotic factors could be potential targets for developing pharmacological therapeutic strategies against DD-associated fibrosis. Full article
(This article belongs to the Special Issue Musculoskeletal Diseases: From Molecular Basis to Therapy)
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10 pages, 1479 KiB  
Article
Natural Compounds That Enhance Motor Function in a Mouse Model of Muscle Fatigue
by Shuichi Shibuya, Kenji Watanabe, Daiki Sakuraba, Takuya Abe and Takahiko Shimizu
Biomedicines 2022, 10(12), 3073; https://doi.org/10.3390/biomedicines10123073 - 29 Nov 2022
Cited by 1 | Viewed by 1931
Abstract
Musculoskeletal disease can be a serious condition associated with aging that may lead to fractures and a bedridden state due to decreased motor function. In addition to exercise training to increase muscle mass, increasing muscle function with the intake of functional foods is [...] Read more.
Musculoskeletal disease can be a serious condition associated with aging that may lead to fractures and a bedridden state due to decreased motor function. In addition to exercise training to increase muscle mass, increasing muscle function with the intake of functional foods is an effective treatment strategy for musculoskeletal disease. Muscle-specific SOD2-deficient mice (muscle-Sod2-/-) show a severe disturbance in exercise in association with increased mitochondrial reactive oxygen species, as well as mitochondrial dysfunction and muscle damage. In the present study, to develop a therapeutic strategy for musculoskeletal disease, we searched for substances that enhanced motor function among functional compounds by in vivo screening using muscle-Sod2-/- mice as a muscle fatigue model. We administered 96 compounds, including antioxidants, to muscle-Sod2-/- mice and assessed their effects on treadmill performance. Among the administered compounds, gossypin, genistein, kaempferol, taxifolin, fumaric acid, β-hydroxy-β-methylbutyrate Ca, and astaxanthin, which are dietary functional food factors, increased forced running time in muscle-Sod2-/- mice. In addition, troglitazone, tempol, trolox, and MnTE-2-PyP, which are antioxidants, also significantly increased the running ability of muscle-Sod2-/- mice. These results suggest that the intake of functional foods with antioxidant activity can improve motor function. Muscle-Sod2-/- mice, as a muscle fatigue model, are suitable for the in vivo screening of functional substances that promote improvements in exercise and muscle performance. Full article
(This article belongs to the Special Issue Musculoskeletal Diseases: From Molecular Basis to Therapy)
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16 pages, 2212 KiB  
Article
Effectiveness of Physiotherapy in the Treatment of Temporomandibular Joint Dysfunction and the Relationship with Cervical Spine
by Maria Daniela Crăciun, Oana Geman, Florin Valentin Leuciuc, Iulian Ştefan Holubiac, Daniela Gheorghiţă and Florin Filip
Biomedicines 2022, 10(11), 2962; https://doi.org/10.3390/biomedicines10112962 - 17 Nov 2022
Cited by 14 | Viewed by 5243
Abstract
Temporomandibular dysfunctions are a heterogeneous group of conditions involving the temporomandibular joints (TMJs) and periarticular musculoskeletal structures. This study aimed to evaluate the effectiveness of a physiotherapy program for TMJ dysfunctions and the relationship with cervical spine. The study design was a non-randomized [...] Read more.
Temporomandibular dysfunctions are a heterogeneous group of conditions involving the temporomandibular joints (TMJs) and periarticular musculoskeletal structures. This study aimed to evaluate the effectiveness of a physiotherapy program for TMJ dysfunctions and the relationship with cervical spine. The study design was a non-randomized clinical trial with two parallel treatment groups: 33 subjects in the experimental group that underwent conservative drug treatment and physiotherapy treatment, and 31 subjects in the control group that underwent only conservative drug treatment. The participants were examined at baseline and re-examined after 3 months. In this study there was a higher incidence of female subjects. After 3 months of treatment of the TMJs and cervical spine, pain decreased in both groups (p = 0001). Muscle testing at the cervical spine and temporomandibular level showed a decrease in pain and muscles spasms. The average percentage values of the Neck Disability Index (NDI) and the Jaw Functional Limitation Scale 8 (JFLS 8) decreased significantly in both groups, but especially in the experimental group (p = 0.001). Physiotherapy treatments could maintain the functional state at the temporomandibular and cervical levels, thus contributing to increasing the quality of daily life. Full article
(This article belongs to the Special Issue Musculoskeletal Diseases: From Molecular Basis to Therapy)
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16 pages, 2845 KiB  
Article
Quantification of Grapiprant and Its Stability Testing under Changing Environmental Conditions
by Paweł Gumułka, Monika Tarsa, Monika Dąbrowska and Małgorzata Starek
Biomedicines 2022, 10(11), 2821; https://doi.org/10.3390/biomedicines10112821 - 5 Nov 2022
Cited by 3 | Viewed by 2667
Abstract
Grapiprant is a new analgesic and anti-inflammatory drug belonging to the piprant class, approved in 2016 by the FDA Veterinary Medicine Center for the treatment of pain and inflammation associated with osteoarthritis in dogs. It acts as a highly selective antagonist of the [...] Read more.
Grapiprant is a new analgesic and anti-inflammatory drug belonging to the piprant class, approved in 2016 by the FDA Veterinary Medicine Center for the treatment of pain and inflammation associated with osteoarthritis in dogs. It acts as a highly selective antagonist of the EP4 receptor, one of the four prostaglandin E2 (PGE2) receptor subtypes. It has been shown to have anti-inflammatory effects in rat models of acute and chronic inflammation and clinical studies in people with osteoarthritis. The current state of knowledge suggests the possibility of using it in oncological therapy. The manuscript presents the development of conditions for the identification and quantitative determination of grapiprant by thin-layer chromatography with densitometric detection. The optimal separation of the substance occurs using silica gel 60F254 chromatographic plates and the mobile phase containing ethyl acetate-toluene-butylamine. Validation (according to ICH requirements) showed that the developed method is characterized by straightness of results in a wide concentration range with the limit of detection of 146.65 µg/mL. The %RSD values of the precision and accuracy confirm the sensitivity and reliability of the developed procedure. Next, the method was used for quantification of grapiprant in a pharmaceutical preparation, and for stability studies under various environmental conditions. Additionally, the mass studies were carried out on the stressed samples using the UPLC-MS/MS method. The degradation products were primarily characterized by comparing their mass fragmentation profiles with those of the drug. The results indicated a potential degradation pathway for grapiprant. Full article
(This article belongs to the Special Issue Musculoskeletal Diseases: From Molecular Basis to Therapy)
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13 pages, 3639 KiB  
Article
Biophysical Stimulation in Delayed Fracture Healing of Hand Phalanx: A Radiographic Evaluation
by Francesco De Francesco, Pasquale Gravina, Stefano Varagona, Stefania Setti, Antonio Gigante and Michele Riccio
Biomedicines 2022, 10(10), 2519; https://doi.org/10.3390/biomedicines10102519 - 9 Oct 2022
Cited by 4 | Viewed by 1818
Abstract
Phalangeal fractures are common events among the upper limbs accounting for 10% of all human body fractures. Fracture complete healing process may persevere several months or years. Most phalangeal fractures present favorable union within 3 to 6 weeks. In the literature, biophysical stimulation [...] Read more.
Phalangeal fractures are common events among the upper limbs accounting for 10% of all human body fractures. Fracture complete healing process may persevere several months or years. Most phalangeal fractures present favorable union within 3 to 6 weeks. In the literature, biophysical stimulation has yielded favorable outcomes in the treatment of hand fractures. A survey involving hospitals in the US reported the use of biophysical stimulation (72%) in relation to nonhealing fractures at three months after trauma. A noninvasive procedure such as biophysical stimulation may be preferential prior to consideration of invasive procedures. In this retrospective study, we analyzed 80 phalangeal fractures, 43 of which did not show any radiographic sign of healing 30 days after surgery; on radiograms, we calculated radiographic data and the total active motion (TAM) for clinical comparison. All radiographic images were evaluated using Adobe Photoshop CS3 (version 10.0, Adobe Systems Inc., San Jose, CA, USA). We calculated the index of relative bone healing each month after surgery starting from 30 days, which was considered as T1, and followed up for a total of 6 months after stimulation (T6) with better results in stimulated groups. We concluded that prompt administration of biophysical stimulation supports fracture healing and yields an important improvement in the union rate compared with nontreatment. Above all, our patients experienced less injury-related distress between the fracture and repair period, which consequently reduced immobilization time, envisaging an early rehabilitation interval, with a better patient hand outcome. Full article
(This article belongs to the Special Issue Musculoskeletal Diseases: From Molecular Basis to Therapy)
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Review

Jump to: Editorial, Research, Other

22 pages, 979 KiB  
Review
Biomechanics of Chondrocytes and Chondrons in Healthy Conditions and Osteoarthritis: A Review of the Mechanical Characterisations at the Microscale
by Sofia Pettenuzzo, Alessandro Arduino, Elisa Belluzzi, Assunta Pozzuoli, Chiara Giulia Fontanella, Pietro Ruggieri, Valentina Salomoni, Carmelo Majorana and Alice Berardo
Biomedicines 2023, 11(7), 1942; https://doi.org/10.3390/biomedicines11071942 - 8 Jul 2023
Cited by 30 | Viewed by 3299
Abstract
Biomechanical studies are expanding across a variety of fields, from biomedicine to biomedical engineering. From the molecular to the system level, mechanical stimuli are crucial regulators of the development of organs and tissues, their growth and related processes such as remodelling, regeneration or [...] Read more.
Biomechanical studies are expanding across a variety of fields, from biomedicine to biomedical engineering. From the molecular to the system level, mechanical stimuli are crucial regulators of the development of organs and tissues, their growth and related processes such as remodelling, regeneration or disease. When dealing with cell mechanics, various experimental techniques have been developed to analyse the passive response of cells; however, cell variability and the extraction process, complex experimental procedures and different models and assumptions may affect the resulting mechanical properties. For these purposes, this review was aimed at collecting the available literature focused on experimental chondrocyte and chondron biomechanics with direct connection to their biochemical functions and activities, in order to point out important information regarding the planning of an experimental test or a comparison with the available results. In particular, this review highlighted (i) the most common experimental techniques used, (ii) the results and models adopted by different authors, (iii) a critical perspective on features that could affect the results and finally (iv) the quantification of structural and mechanical changes due to a degenerative pathology such as osteoarthritis. Full article
(This article belongs to the Special Issue Musculoskeletal Diseases: From Molecular Basis to Therapy)
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17 pages, 1268 KiB  
Review
Osteosarcopenia and Pain: Do We Have a Way Out?
by Roberto Bonanni, Sonia Gino Grillo, Ida Cariati, Lucia Tranquillo, Riccardo Iundusi, Elena Gasbarra, Virginia Tancredi and Umberto Tarantino
Biomedicines 2023, 11(5), 1285; https://doi.org/10.3390/biomedicines11051285 - 26 Apr 2023
Cited by 9 | Viewed by 2303
Abstract
Osteosarcopenia (OSP) is a geriatric syndrome characterized by the coexistence of osteoporosis and sarcopenia and associated with an increased risk of fragility fractures, disability, and mortality. For patients with this syndrome, musculoskeletal pain represents the most significant challenge since, in addition to limiting [...] Read more.
Osteosarcopenia (OSP) is a geriatric syndrome characterized by the coexistence of osteoporosis and sarcopenia and associated with an increased risk of fragility fractures, disability, and mortality. For patients with this syndrome, musculoskeletal pain represents the most significant challenge since, in addition to limiting the individual’s functionality and promoting disability, it has a huge psychological burden involving anxiety, depression, and social withdrawal. Unfortunately, the molecular mechanisms involved in the development and persistence of pain in OSP have not yet been fully elucidated, although immune cells are known to play a key role in these processes. Indeed, they release several molecules that promote persistent inflammation and nociceptive stimulation, resulting in the gating of ion channels responsible for the generation and propagation of the noxious stimulus. The adoption of countermeasures to counteract the OSP progression and reduce the algic component appears to be necessary, providing patients with a better quality of life and greater adherence to treatment. In addition, the development of multimodal therapies, based on an interdisciplinary approach, appears to be crucial, combining the use of anti-osteoporotic drugs with an educational programme, regular physical activity, and proper nutrition to eliminate risk factors. Based on this evidence, we conducted a narrative review using the PubMed and Google Scholar search engines to summarize the current knowledge on the molecular mechanisms involved in the pain development in OSP and the potential countermeasures to be taken. The lack of studies addressing this topic highlights the need to conduct new research into the resolution of an ever-expanding social problem. Full article
(This article belongs to the Special Issue Musculoskeletal Diseases: From Molecular Basis to Therapy)
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16 pages, 2440 KiB  
Review
Role of Matrix Metalloproteinases in Musculoskeletal Diseases
by Lokender Kumar, Monish Bisen, Azhar Khan, Pradeep Kumar and Sanjay Kumar Singh Patel
Biomedicines 2022, 10(10), 2477; https://doi.org/10.3390/biomedicines10102477 - 4 Oct 2022
Cited by 17 | Viewed by 3090
Abstract
Musculoskeletal disorders include rheumatoid arthritis, osteoarthritis, sarcopenia, injury, stiffness, and bone loss. The prevalence of these conditions is frequent among elderly populations with significant mobility and mortality rates. This may lead to extreme discomfort and detrimental effect on the patient’s health and socioeconomic [...] Read more.
Musculoskeletal disorders include rheumatoid arthritis, osteoarthritis, sarcopenia, injury, stiffness, and bone loss. The prevalence of these conditions is frequent among elderly populations with significant mobility and mortality rates. This may lead to extreme discomfort and detrimental effect on the patient’s health and socioeconomic situation. Muscles, ligaments, tendons, and soft tissue are vital for body function and movement. Matrix metalloproteinases (MMPs) are regulatory proteases involved in synthesizing, degrading, and remodeling extracellular matrix (ECM) components. By modulating ECM reconstruction, cellular migration, and differentiation, MMPs preserve myofiber integrity and homeostasis. In this review, the role of MMPs in skeletal muscle function, muscle injury and repair, skeletal muscle inflammation, and muscular dystrophy and future approaches for MMP-based therapies in musculoskeletal disorders are discussed at the cellular and molecule level. Full article
(This article belongs to the Special Issue Musculoskeletal Diseases: From Molecular Basis to Therapy)
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Other

13 pages, 633 KiB  
Systematic Review
Quantitative Ultrasound and Bone Health in Elderly People, a Systematic Review
by Isabel Escobio-Prieto, María Blanco-Díaz, Elena Pinero-Pinto, Alvaro Manuel Rodriguez-Rodriguez, Francisco Javier Ruiz-Dorantes and Manuel Albornoz-Cabello
Biomedicines 2023, 11(4), 1175; https://doi.org/10.3390/biomedicines11041175 - 13 Apr 2023
Cited by 4 | Viewed by 2100
Abstract
Reduced bone mineral density (BMD), osteoporosis, and their associated fractures are one of the main musculoskeletal disorders of the elderly. Quickness in diagnosis could prevent associated complications in these people. This study aimed to perform a systematic review (SR) to analyze and synthesize [...] Read more.
Reduced bone mineral density (BMD), osteoporosis, and their associated fractures are one of the main musculoskeletal disorders of the elderly. Quickness in diagnosis could prevent associated complications in these people. This study aimed to perform a systematic review (SR) to analyze and synthesize current research on whether a calcaneal quantitative ultrasound (QUS) can estimate BMD and predict fracture risk in elderly people compared to dual-energy x-ray absorptiometry (DXA), following the PRISMA guidelines. A search was conducted in the main open-access health science databases: PubMed and Web of Science (WOS). DXA is the gold standard for the diagnosis of osteoporosis. Despite controversial results, it can be concluded that the calcaneal QUS tool may be a promising method to evaluate BMD in elderly people, facilitating its prevention and diagnosis. However, further studies are needed to validate the use of calcaneal QUS. Full article
(This article belongs to the Special Issue Musculoskeletal Diseases: From Molecular Basis to Therapy)
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28 pages, 3041 KiB  
Systematic Review
Insights into Pathogenesis, Nutritional and Drug Approach in Sarcopenia: A Systematic Review
by Rodrigo Haber Mellen, Otávio Simões Girotto, Eduarda Boni Marques, Lucas Fornari Laurindo, Paulo Cesar Grippa, Claudemir Gregório Mendes, Lorena Natalino Haber Garcia, Marcelo Dib Bechara, Sandra Maria Barbalho, Renata Vargas Sinatora, Jesselina Francisco dos Santos Haber, Uri Adrian P. Flato, Patricia Cincotto dos Santos Bueno, Claudia Rucco Penteado Detregiachi and Karina Quesada
Biomedicines 2023, 11(1), 136; https://doi.org/10.3390/biomedicines11010136 - 5 Jan 2023
Cited by 33 | Viewed by 9879
Abstract
Sarcopenia is a multifactorial condition related to the loss of muscle mass and strength due to aging, eating habits, physical inactivity, or even caused by another disease. Affected individuals have a higher risk of falls and may be associated with heart disease, respiratory [...] Read more.
Sarcopenia is a multifactorial condition related to the loss of muscle mass and strength due to aging, eating habits, physical inactivity, or even caused by another disease. Affected individuals have a higher risk of falls and may be associated with heart disease, respiratory diseases, cognitive impairment, and consequently an increased risk of hospitalization, in addition to causing an economic impact due to the high cost of care during the stay in hospitals. The standardization of appropriate treatment for patients with sarcopenia that could help reduce pathology-related morbidity is necessary. For these reasons, this study aimed to perform a systematic review of the role of nutrition and drugs that could ameliorate the health and quality of life of sarcopenic patients and PRISMA guidelines were followed. Lifestyle interventions have shown a profound impact on sarcopenia treatment but using supplements and different drugs can also impact skeletal muscle maintenance. Creatine, leucine, branched-chain amino acids, omega 3, and vitamin D can show benefits. Although with controversial results, medications such as Metformin, GLP-1, losartan, statin, growth hormone, and dipeptidyl peptidase 4 inhibitors have also been considered and can alter the sarcopenic’s metabolic parameters, protect against cardiovascular diseases and outcomes, while protecting muscles. Full article
(This article belongs to the Special Issue Musculoskeletal Diseases: From Molecular Basis to Therapy)
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