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Musculoskeletal Diseases: From Molecular Basis to Therapy (Volume II)

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A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: 30 September 2024 | Viewed by 12765

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Special Issue Editors

Dr. Elisa Belluzzi

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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

Dr. Assunta Pozzuoli

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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

Manuscript Submission Information

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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

Published Papers (13 papers)

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Research

Jump to: Review

11 pages, 807 KiB

Open AccessArticle

Relationship of Hematological Profiles with the Serum Complement System in Patients with Systemic Lupus Erythematosus

by Yolanda Fernández-Cladera, María García-González, Marta Hernández-Díaz, Fuensanta Gómez-Bernal, Juan C. Quevedo-Abeledo, Agustín F. González-Rivero, Antonia de Vera-González, Cristina Gómez-Moreno, Miguel Á. González-Gay and Iván Ferraz-Amaro

Biomedicines 2024, 12(5), 967; https://doi.org/10.3390/biomedicines12050967 - 27 Apr 2024

Viewed by 399

Abstract

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder identified by hematological abnormalities including anemia, leukopenia, and thrombocytopenia. Complement system disturbance is implicated in the pathogenesis of SLE. In this work, we aim to study how a full assessment of the complement system, which includes the evaluation of its three pathways, relates to blood cell counts in a population of patients with SLE. New-generation functional assays of the classical, alternative, and lectin pathways of the complement system were conducted in 284 patients with SLE. Additionally, serum levels of inactive molecules (C1q, C2, C3, C4, factor D) and activated molecules (C3a), as well as regulators (C1-inhibitor and factor H), were evaluated. Complete blood cell counts were analyzed. Multivariable linear regression analysis was performed to study the relationship of hematological profiles with this full characterization of the complement system. After multivariable adjustments that included age, sex, SLICC-DI (damage), and SLEDAI (activity) scores, as well as the use of aspirin, prednisone, methotrexate, azathioprine, and mycophenolate mofetil, several relationships were observed between the C pathways and the individual products and blood cells profile. Lower values of C1q and C2 were associated with lower hemoglobin levels. Lower leukocyte counts showed significantly lower values of C4, C1 inhibitor, C3, factor D, and alternative pathway functional levels. Neutrophil counts showed significant negative relationships only with the alternative pathway and C1-inh. In the case of lymphocytes, associations were found, especially with functional tests of the classical and alternative pathways, as well as with C2, C4, C3, and C3a. On the contrary, for platelets, significance was only observed, after multivariable adjustment, with lower C2 concentrations. In conclusion, the serum complement system and hematological profile in SLE are independently linked, after adjustment for disease activity and damage. These relationships are basically negative and are predominantly found in lymphocytes. Full article

(This article belongs to the Special Issue Musculoskeletal Diseases: From Molecular Basis to Therapy (Volume II))

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15 pages, 2330 KiB

Open AccessArticle

Higher Synovial Immunohistochemistry Reactivity of IL-17A, Dkk1, and TGF-β1 in Patients with Early Psoriatic Arthritis and Rheumatoid Arthritis Could Predict the Use of Biologics

by Jose A. Pinto-Tasende, Mercedes Fernandez-Moreno, Ignacio Rego Perez, J. Carlos Fernandez-Lopez, Natividad Oreiro-Villar, F. Javier De Toro Santos and Francisco J. Blanco-García

Biomedicines 2024, 12(4), 815; https://doi.org/10.3390/biomedicines12040815 - 8 Apr 2024

Viewed by 661

Abstract

Background: Delay in diagnosis and therapy in patients with arthritis commonly leads to progressive articular damage. The study aimed to investigate the immunohistochemical reactivity of synovial cytokines associated with inflammation and the bone erosives/neoformatives processes among individuals diagnosed with psoriatic arthritis (PsA), rheumatoid arthritis (RA), osteoarthritis (OA), and radiographic axial spondyloarthritis (r-axSpA), with the intention of identifying potential biomarkers. Methods: Specimens were collected from the inflamed knee joints of patients referred for arthroscopic procedures, and the synovial tissue (ST) was prepared for quantifying protein expression through immunohistochemical analysis (% expressed in Ratio_Area-Intensity) for TGF-β1, IL-17A, Dkk1, BMP2, BMP4, and Wnt5b. The collected data underwent thorough analysis and examination of their predictive capabilities utilising receiver operating characteristic (ROC) curves. Results: Valid synovial tissue samples were acquired from 40 patients for IHC quantification analysis. Initially, these patients had not undergone treatment with biologics. However, after 5 years, 4 out of 13 patients diagnosed with PsA and two out of nine patients diagnosed with RA had commenced biologic treatments. Individuals with early PsA who received subsequent biologic treatment exhibited significantly elevated IHC reactivity in ST for TGF-β1 (p = 0.015). Additionally, patients with both PsA and RA who underwent biologic therapy displayed increased IHC reactivity for IL-17A (p = 0.016), TGF-β1 (p = 0.009), and Dkk1 (p = 0.042). ROC curve analysis of IHC reactivity for TGF-β1, Dkk1, and IL-17A in the synovial seems to predict future treatment with biologics in the next 5 years with the area under the curve (AUC) of a combined sum of the three values: AUC: 0.828 (95% CI: 0.689–0.968; p 0.005) S 75% E 84.4%. Conclusions: Higher synovial immunohistochemistry reactivity of IL-17A, Dkk1, and TGF-β1 in patients with early psoriatic arthritis and rheumatoid arthritis may serve as potential indicators for predicting the necessity of utilising biologic treatments. Full article

(This article belongs to the Special Issue Musculoskeletal Diseases: From Molecular Basis to Therapy (Volume II))

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12 pages, 535 KiB

Open AccessArticle

The Genetic Markers of Knee Osteoarthritis in Women from Russia

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

Biomedicines 2024, 12(4), 782; https://doi.org/10.3390/biomedicines12040782 - 2 Apr 2024

Viewed by 514

Abstract

Osteoarthritis is a chronic progressive joint disease that clinically debuts at the stage of pronounced morphologic changes, which makes treatment difficult. In this regard, an important task is the study of genetic markers of the disease, which have not been definitively established, due to the clinical and ethnic heterogeneity of the studied populations. To find the genetic markers for the development of knee osteoarthritis (OA) in women from the Volga-Ural region of Russia, we conducted research in two stages using different genotyping methods, such as the restriction fragment length polymorphism (RFLP) measurement, TaqMan technology and competitive allele-specific PCR—KASP^TM. In the first stage, we studied polymorphic variants of candidate genes (ACAN, ADAMTS5, CHST11, SOX9, COL1A1) for OA development. The association of the *27 allele of the VNTR locus of the ACAN gene was identified (OR = 1.6). In the second stage, we replicated the GWAS results (ASTN2, ALDH1A2, DVWA, CHST11, GNL3, NCOA3, FILIP/SENP1, MCF2L, GLT8D, DOT1L) for knee OA studies. The association of the *T allele of the rs7639618 locus of the DVWA gene was detected (OR = 1.54). Thus, the VNTR locus of ACAN and the rs7639618 locus of DVWA are risk factors for knee OA in women from the Volga-Ural region of Russia. Full article

(This article belongs to the Special Issue Musculoskeletal Diseases: From Molecular Basis to Therapy (Volume II))

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14 pages, 2383 KiB

Open AccessArticle

Conditioned Medium of Intervertebral Disc Cells Inhibits Osteo-Genesis on Autologous Bone-Marrow-Derived Mesenchymal Stromal Cells and Osteoblasts

by Shuimu Chen, Andreas S. Croft, Sebastian Bigdon, Christoph E. Albers, Zhen Li and Benjamin Gantenbein

Biomedicines 2024, 12(2), 376; https://doi.org/10.3390/biomedicines12020376 - 6 Feb 2024

Viewed by 891

Abstract

Low back pain (LBP) is associated with the degeneration of human intervertebral discs (IVDs). Despite progress in the treatment of LBP through spinal fusion, some cases still end in non-fusion after the removal of the affected IVD tissue. In this study, we investigated the hypothesis that the remaining IVD cells secrete BMP inhibitors that are sufficient to inhibit osteogenesis in autologous osteoblasts (OBs) and bone marrow mesenchymal stem cells (MSCs). A conditioned medium (CM) from primary human IVD cells in 3D alginate culture was co-cultured with seven donor-matched OB and MSCs. After ten days, osteogenesis was quantified at the transcript level using qPCR to measure the expression of bone-related genes and BMP antagonists, and at the protein level by alkaline phosphatase (ALP) activity. Additionally, cells were evaluated histologically using alizarin red (ALZR) staining on Day 21. For judging ALP activity and osteogenesis, the Noggin expression in samples was investigated to uncover the potential causes. The results after culture with the CM showed significantly decreased ALP activity and the inhibition of the calcium deposit formation in alizarin red staining. Interestingly, no significant changes were found among most bone-related genes and BMP antagonists in OBs and MSCs. Noteworthy, Noggin was relatively expressed higher in human IVD cells than in autologous OBs or MSCs (relative to autologous OB, the average fold change was in 6.9, 10.0, and 6.3 in AFC, CEPC, and NPC, respectively; and relative to autologous MSC, the average fold change was 2.3, 3.4, and 3.2, in AFC, CEPC, and NPC, respectively). The upregulation of Noggin in residual human IVDs could potentially inhibit the osteogenesis of autologous OB and MSC, thus inhibiting the postoperative spinal fusion after discectomy surgery. Full article

(This article belongs to the Special Issue Musculoskeletal Diseases: From Molecular Basis to Therapy (Volume II))

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14 pages, 1794 KiB

Open AccessArticle

Impact of Long-Term Swimming Exercise on Rat Femur Bone Quality

by Laura Freitas, Andrea Bezerra, Ana Resende-Coelho, Maria Gomez-Lazaro, Leonardo Maciel, Tânia Amorim, Ricardo J. Fernandes and Hélder Fonseca

Biomedicines 2024, 12(1), 35; https://doi.org/10.3390/biomedicines12010035 - 22 Dec 2023

Viewed by 831

Abstract

Considering the conflicting evidence regarding the potential long-term detrimental effect of swimming during growth on femur quality and fracture risk, our aim was to investigate the effect of eight months of swimming on femur quality. Twenty male eight-week-old Wistar rats were assigned into a swimming (SW; n = 10; 2 h/day, 5 days/week) or active control group (CG; n = 10, housed with running wheel) for eight months. Plasma osteocalcin and C-terminal telopeptide of type I collagen concentrations (ELISA) were assessed at baseline, four, and eight months of protocol. Femur structure (micro-computed tomography), biomechanical properties (three-point bending), and cellular density (histology) were determined after the protocol. SW displayed a lower uncoupling index, suggesting higher bone resorption, lower empty lacunae density, cortical and trabecular femur mass, femur length and cortical thickness, and higher cortical porosity than CG (p < 0.05). Although both biomarkers’ concentrations decreased in both groups throughout the experiment (p < 0.001), there were no significant differences between groups (p > 0.05). No differences were also found regarding biomechanical properties, bone marrow adiposity, and osteocyte and osteoclast densities (p > 0.05). Long-term swimming was associated with unbalanced bone turnover and compromised femur growth, lower femur mass, and deteriorated cortical bone microarchitecture. However, femur trabecular microarchitecture and biomechanical properties were not affected by swimming. Full article

(This article belongs to the Special Issue Musculoskeletal Diseases: From Molecular Basis to Therapy (Volume II))

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11 pages, 1564 KiB

Open AccessArticle

Cervical Sagittal Balance: Impact on Clinical Outcomes and Subsidence in Anterior Cervical Discectomy and Fusion

by Adam Bębenek, Maciej Dominiak and Bartosz Godlewski

Biomedicines 2023, 11(12), 3310; https://doi.org/10.3390/biomedicines11123310 - 14 Dec 2023

Viewed by 661

Abstract

Degenerative disease of the cervical spine leads to sagittal imbalance, which may affect treatment results. The purpose of this study was to evaluate changes in selected cervical sagittal balance parameters and their effects on subsidence and clinical outcomes of the procedure. This study encompassed a total of 95 evaluated patients who underwent anterior cervical discectomy and fusion (ACDF). Selected cervical sagittal balance parameters were assessed using lateral projection X-rays: C2–C7 spinal vertical axis (C2–C7 SVA), spinocranial angle (SCA), C7 slope, C2–C7 lordosis, and the segmental Cobb angle. Measurements were collected the day before, the day after, and 12 months after surgery. Changes in clinical parameters was assessed using the VAS and NDI scales. Subsidence was defined as a loss of intervertebral height of more than 30% of the baseline value. Among all the assessed parameters, only the C2–C7 SVA demonstrated a statistically significant difference between the groups with and without subsidence: 26.03 vs. 21.79 [mm], with p = 0.0182, preoperatively and 27.80 vs. 24.94 [mm], with p = 0.0449, on the day after surgery, respectively. We conclude that higher preoperative and postoperative C2–C7 SVA values might contribute to an elevated risk of implant subsidence. Furthermore, both the SCA and C7 slope could conceivably influence the clinical outcome, respectively impacting pain, as assessed by the VAS and the disability, as evaluated through the NDI scale. Full article

(This article belongs to the Special Issue Musculoskeletal Diseases: From Molecular Basis to Therapy (Volume II))

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17 pages, 3754 KiB

Open AccessArticle

The Ultraviolet Irradiation of Keratinocytes Induces Ectopic Expression of LINE-1 Retrotransposon Machinery and Leads to Cellular Senescence

by Fadi Touma, Marine Lambert, Amelia Martínez Villarreal, Jennifer Gantchev, Brandon Ramchatesingh and Ivan V. Litvinov

Biomedicines 2023, 11(11), 3017; https://doi.org/10.3390/biomedicines11113017 - 10 Nov 2023

Viewed by 1043

Abstract

Retrotransposons have played an important role in evolution through their transposable activity. The largest and the only currently active human group of mobile DNAs are the LINE-1 retrotransposons. The ectopic expression of LINE-1 has been correlated with genomic instability. Narrow-band ultraviolet B (NB-UVB) and broad-band ultraviolet B (BB-UVB) phototherapy is commonly used for the treatment of dermatological diseases. UVB exposure is carcinogenic and can lead, in keratinocytes, to genomic instability. We hypothesize that LINE-1 reactivation occurs at a high rate in response to UVB exposure on the skin, which significantly contributes to genomic instability and DNA damage leading to cellular senescence and photoaging. Immortalized N/TERT1 and HaCaT human keratinocyte cell lines were irradiated in vitro with either NB-UVB or BB-UVB. Using immunofluorescence and Western blotting, we confirmed UVB-induced protein expression of LINE-1. Using RT-qPCR, we measured the mRNA expression of LINE-1 and senescence markers that were upregulated after several NB-UVB exposures. Selected miRNAs that are known to bind LINE-1 mRNA were measured using RT-qPCR, and the expression of miR-16 was downregulated with UVB exposure. Our findings demonstrate that UVB irradiation induces LINE-1 reactivation and DNA damage in normal keratinocytes along with the associated upregulation of cellular senescence markers and change in miR-16 expression. Full article

(This article belongs to the Special Issue Musculoskeletal Diseases: From Molecular Basis to Therapy (Volume II))

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15 pages, 3602 KiB

Open AccessArticle

Potential Joint Protective and Anti-Inflammatory Effects of Integrin α_vβ₃ in IL-1β-Treated Chondrocytes Cells

by Hun Hwan Kim, Se Hyo Jeong, Min Yeong Park, Pritam Bhagwan Bhosale, Abuyaseer Abusaliya, Hyun Wook Kim, Je Kyung Seong, Meejung Ahn, Kwang Il Park, Jeong Doo Heo, Young Sil Kim and Gon Sup Kim

Biomedicines 2023, 11(10), 2745; https://doi.org/10.3390/biomedicines11102745 - 10 Oct 2023

Viewed by 1284

Abstract

In osteoarthritis (OA), the articular cartilage covering the articular surface of the bone wears out, exposing the subchondral bone, and the synovial membrane surrounding the joint becomes inflamed, causing pain and deformity. OA causes pain, stiffness, and swelling, and discomfort in the knee when climbing stairs is a typical symptom. Although drug development studies are conducted to treat these inflammatory joint diseases, it is difficult to find conclusive research results which could reduce inflammation and slow cartilage tear. The development of drugs to relieve inflammatory pain often utilizes inflammatory triggers. Interleukins, one of the proteins in the limelight as pro-inflammatory factors, are immune-system-stimulating factors that promote the body’s fight against harmful factors such as bacteria. In this study, inflammation was induced in Chondrocytes cells (Chon-001 cells) with IL-1β and then treated with integrin α_vβ₃ to show anti-inflammatory and chondrogenesis effects. Integrin α_vβ₃ was not toxic to Chon-001 cells in any concentration groups treated with or without IL-1β. COX-2 and iNOS, which are major markers of inflammation, were significantly reduced by integrin α_vβ₃ treatment. Expressions of p-ERK, p-JNK, and p-p38 corresponding to the MAPKs signaling pathway and p-IκBα and p-p65 corresponding to the NF-κB signaling pathway were also decreased in a dose-dependent manner upon integrin α_vβ₃ treatment, indicating that inflammation was inhibited, whereas treatment with integrin α_vβ₃ significantly increased the expression of ALP, RUNX2, BMP2, BMP4, Aggrecan, SOX9, and COL2A1, suggesting that osteogenesis and chondrogenesis were induced. These results suggest that integrin α_vβ₃ in-duces an anti-inflammatory effect, osteogenesis, and chondrogenesis on IL-1β-induced Chon-001 cells. Full article

(This article belongs to the Special Issue Musculoskeletal Diseases: From Molecular Basis to Therapy (Volume II))

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13 pages, 3192 KiB

Open AccessArticle

Effect of Calcitriol and Vitamin D Receptor Modulator 2 on Recovery of Injured Skeletal Muscle in Wistar Rats

by Ioannis Stratos, Svenja Schleese, Ingmar Rinas, Brigitte Vollmar and Thomas Mittlmeier

Biomedicines 2023, 11(9), 2477; https://doi.org/10.3390/biomedicines11092477 - 7 Sep 2023

Viewed by 843

Abstract

Muscle injuries often result in functional limitations due to insufficient healing. This study assessed the influence of calcitriol and vitamin D Receptor Modulator 2 (VDRM2) on muscle regeneration in male Wistar rats following open blunt muscle injury. The injured left soleus muscle of the rats was treated for the first four days after trauma with local injections of either calcitriol, VDRM2, or a 10% ethanol solution (control). Although muscle strength significantly decreased post-injury, all groups showed gradual improvement but did not achieve full recovery. By the 14th day, calcitriol-treated rats significantly outperformed the control group in the incomplete tetanic force, with VDRM2-treated rats showing muscle strength values that fell between the control and calcitriol groups. Similar trends were observed in complete tetanic contractions and were confirmed histologically via muscle cell width quantification. Additionally, histological analysis showed increased cellular turnover on the fourth postoperative day in the calcitriol group, as indicated by elevated cell proliferation rates and fewer apoptotic cells. VDRM2-treated animals showed only an increased proliferative activity on day 4 after injury. No noticeable differences between the groups for CAE-positive cells or visible muscle tissue area were found. In conclusion, predominantly calcitriol positively influenced post-trauma muscle recovery, where VDRM2 had substantially lower biological activity. Full article

(This article belongs to the Special Issue Musculoskeletal Diseases: From Molecular Basis to Therapy (Volume II))

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15 pages, 2081 KiB

Open AccessArticle

Characterization of the Ang/Tie2 Signaling Pathway in the Diaphragm Muscle of DMD Mice

by Yiming Lin, Andrew McClennan and Lisa Hoffman

Biomedicines 2023, 11(8), 2265; https://doi.org/10.3390/biomedicines11082265 - 14 Aug 2023

Cited by 1 | Viewed by 1108

Abstract

In Duchenne muscular dystrophy (DMD), angiogenesis appears to be attenuated. Local administration of angiopoietin 1 (Ang1) has been shown to reduce inflammation, ischemia, and fibrosis in DMD mice. Ang1 is a vital vascular stabilizing factor that activates the endothelial cell receptor Tie2, leading to downstream pro-survival PI3K/Akt pathway activation and eNOS phosphorylation. In this study, we aimed to characterize the Ang/Tie2 signaling pathway within the diaphragm muscle of mouse models of DMD. Utilizing ELISA, immunoblots, and RT-qPCR, we demonstrated that Ang1 was downregulated, while the antagonist angiopoietin 2 (Ang2) was upregulated, leading to a decreased Ang1/Ang2 ratio. This correlated with a reduction in the phosphorylated Tie2/total Tie2 ratio. Interestingly, no significant differences in Akt or eNOS phosphorylation were observed, although DMD murine models did have elevated total Akt protein concentrations. These observations suggest that Ang1/Tie2 signaling may be dysregulated in the diaphragm muscle of DMD and further investigations may lead to new therapeutic interventions for DMD. Full article

(This article belongs to the Special Issue Musculoskeletal Diseases: From Molecular Basis to Therapy (Volume II))

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Review

Jump to: Research

26 pages, 5045 KiB

Open AccessReview

Applications of Hydrogels in Osteoarthritis Treatment

by Xin Gan, Xiaohui Wang, Yiwan Huang, Guanghao Li and Hao Kang

Biomedicines 2024, 12(4), 923; https://doi.org/10.3390/biomedicines12040923 - 22 Apr 2024

Viewed by 721

Abstract

This review critically evaluates advancements in multifunctional hydrogels, particularly focusing on their applications in osteoarthritis (OA) therapy. As research evolves from traditional natural materials, there is a significant shift towards synthetic and composite hydrogels, known for their superior mechanical properties and enhanced biodegradability. This review spotlights novel applications such as injectable hydrogels, microneedle technology, and responsive hydrogels, which have revolutionized OA treatment through targeted and efficient therapeutic delivery. Moreover, it discusses innovative hydrogel materials, including protein-based and superlubricating hydrogels, for their potential to reduce joint friction and inflammation. The integration of bioactive compounds within hydrogels to augment therapeutic efficacy is also examined. Furthermore, the review anticipates continued technological advancements and a deeper understanding of hydrogel-based OA therapies. It emphasizes the potential of hydrogels to provide tailored, minimally invasive treatments, thus highlighting their critical role in advancing the dynamic field of biomaterial science for OA management. Full article

(This article belongs to the Special Issue Musculoskeletal Diseases: From Molecular Basis to Therapy (Volume II))

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13 pages, 821 KiB

Open AccessReview

Casimersen (AMONDYS 45™): An Antisense Oligonucleotide for Duchenne Muscular Dystrophy

by Milyard Assefa, Addison Gepfert, Meesam Zaheer, Julia M. Hum and Brian W. Skinner

Biomedicines 2024, 12(4), 912; https://doi.org/10.3390/biomedicines12040912 - 20 Apr 2024

Viewed by 782

Abstract

Casimersen (AMONDYS 45^TM) is an antisense oligonucleotide of the phosphorodiamidate morpholino oligomer subclass developed by Sarepta therapeutics. It was approved by the Food and Drug Administration (FDA) in February 2021 to treat Duchenne muscular dystrophy (DMD) in patients whose DMD gene mutation is amenable to exon 45 skipping. Administered intravenously, casimersen binds to the pre-mRNA of the DMD gene to skip a mutated region of an exon, thereby producing an internally truncated yet functional dystrophin protein in DMD patients. This is essential in maintaining the structure of a myocyte membrane. While casimersen is currently continuing in phase III of clinical trials in various countries, it was granted approval by the FDA under the accelerated approval program due to its observed increase in dystrophin production. This article discusses the pathophysiology of DMD, summarizes available treatments thus far, and provides a full drug review of casimersen (AMONDYS 45^TM). Full article

(This article belongs to the Special Issue Musculoskeletal Diseases: From Molecular Basis to Therapy (Volume II))

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24 pages, 977 KiB

Open AccessReview

Implications of siRNA Therapy in Bone Health: Silencing Communicates

by Puneetpal Singh, Monica Singh, Baani Singh, Kirti Sharma, Nitin Kumar, Deepinder Singh, Harpal Singh Klair and Sarabjit Mastana

Biomedicines 2024, 12(1), 90; https://doi.org/10.3390/biomedicines12010090 - 1 Jan 2024

Viewed by 1275

Abstract

The global statistics of bone disorders, skeletal defects, and fractures are frightening. Several therapeutic strategies are being used to fix them; however, RNAi-based siRNA therapy is starting to prove to be a promising approach for the prevention of bone disorders because of its advanced capabilities to deliver siRNA or siRNA drug conjugate to the target tissue. Despite its ‘bench-to-bedside’ usefulness and approval by food and drug administration for five siRNA-based therapeutic medicines: Patisiran, Vutrisiran, Inclisiran, Lumasiran, and Givosiran, its use for the other diseases still remains to be resolved. By correcting the complications and complexities involved in siRNA delivery for its sustained release, better absorption, and toxicity-free activity, siRNA therapy can be harnessed as an experimental tool for the prevention of complex and undruggable diseases with a personalized medicine approach. The present review summarizes the findings of notable research to address the implications of siRNA in bone health for the restoration of bone mass, recovery of bone loss, and recuperation of bone fractures. Full article

(This article belongs to the Special Issue Musculoskeletal Diseases: From Molecular Basis to Therapy (Volume II))

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