-
Journal of ISAKOS : Joint Disorders &... Dec 2023
Topics: Humans; Shoulder; Longevity; Shoulder Joint; Hemiarthroplasty; Osteoarthritis
PubMed: 37913870
DOI: 10.1016/j.jisako.2023.10.012 -
Ugeskrift For Laeger Jan 2024Intraarticular treatment of osteoarthritis with mesenchymal stem cells (MSCs) has shown promising results and is being increasingly implemented in the clinic. Autologous... (Review)
Review
Intraarticular treatment of osteoarthritis with mesenchymal stem cells (MSCs) has shown promising results and is being increasingly implemented in the clinic. Autologous MSCs are the primary source of therapy but issues related to cell expansion, patient age, and acute therapies have opened a need for allogenic MSCs. Problematic immunological reactions such as pain, joint swelling, urticarial, and MSC destruction are, however, reported when using allogenic MSCs at the first to second treatment. Multiple factors need to be considered when deciding on autologous or allogenic MSC treatment, as argued in this review.
Topics: Humans; Mesenchymal Stem Cell Transplantation; Osteoarthritis; Mesenchymal Stem Cells; Pain
PubMed: 38235773
DOI: 10.61409/V06230423 -
Science Advances Dec 2023Musculoskeletal disorders contribute substantially to worldwide disability. Anterior cruciate ligament (ACL) tears result in unresolved muscle weakness and posttraumatic...
Musculoskeletal disorders contribute substantially to worldwide disability. Anterior cruciate ligament (ACL) tears result in unresolved muscle weakness and posttraumatic osteoarthritis (PTOA). Growth differentiation factor 8 (GDF8) has been implicated in the pathogenesis of musculoskeletal degeneration following ACL injury. We investigated GDF8 levels in ACL-injured human skeletal muscle and serum and tested a humanized monoclonal GDF8 antibody against a placebo in a mouse model of PTOA (surgically induced ACL tear). In patients, muscle GDF8 was predictive of atrophy, weakness, and periarticular bone loss 6 months following surgical ACL reconstruction. In mice, GDF8 antibody administration substantially mitigated muscle atrophy, weakness, and fibrosis. GDF8 antibody treatment rescued the skeletal muscle and articular cartilage transcriptomic response to ACL injury and attenuated PTOA severity and deficits in periarticular bone microarchitecture. Furthermore, GDF8 genetic deletion neutralized musculoskeletal deficits in response to ACL injury. Our findings support an opportunity for rapid targeting of GDF8 to enhance functional musculoskeletal recovery and mitigate the severity of PTOA after injury.
Topics: Animals; Humans; Mice; Anterior Cruciate Ligament Injuries; Disease Models, Animal; Muscle, Skeletal; Myostatin; Osteoarthritis
PubMed: 38019905
DOI: 10.1126/sciadv.adi9134 -
Clinical and Translational Medicine Aug 2023Circular RNAs (circRNAs) have risen to prominence as important regulators of biological processes. This study investigated whether circGNB1 functions as a competitive...
BACKGROUND
Circular RNAs (circRNAs) have risen to prominence as important regulators of biological processes. This study investigated whether circGNB1 functions as a competitive endogenous RNA to regulate the pathological process of oxidative stress in age-related osteoarthritis (OA).
METHODS
The relationship between circGNB1 expression and oxidative stress/OA severity was determined in cartilages from OA patients at different ages. The biological roles of circGNB1 in oxidative stress and OA progression, and its downstream targets were determined using gain- and loss-of-function experiments in various biochemical assays in human chondrocytes (HCs). The in vivo effects of circGNB1 overexpression and knockdown were also determined using a destabilization of the medial meniscus (DMM) mouse model.
RESULTS
Increased circGNB1 expression was detected in HCs under oxidative and inflammatory stress and in the cartilage of older individuals. Mechanistically, circGNB1 sponged miR-152-3p and thus blocked its interaction with its downstream mRNA target, ring finger protein 219 (RNF219), which in turn stabilized caveolin-1 (CAV1) by preventing its ubiquitination at the K47 residue. CircGNB1 inhibited IL-10 signalling by antagonizing miR-152-3p-mediated RNF219 and CAV1 inhibition. Consequently, circGNB1 overexpression promoted OA progression by enhancing catabolic factor expression and oxidative stress and by suppressing anabolic genes in vitro and in vivo. Furthermore, circGNB1 knockdown alleviated the severity of OA, whereas circGNB1 overexpression had the opposite effect in a DMM mouse model of OA.
CONCLUSION
CircGNB1 regulated oxidative stress and OA progression via the miR-152-3p/RNF219/CAV1 axis. Modulating circGNB1 could be an effective strategy for treating OA.
Topics: Mice; Animals; Humans; Chondrocytes; MicroRNAs; Cells, Cultured; Apoptosis; Osteoarthritis; Disease Models, Animal; Oxidative Stress
PubMed: 37537733
DOI: 10.1002/ctm2.1358 -
Biomedicine & Pharmacotherapy =... Sep 2023HYBID is a new hyaluronan-degrading enzyme and exists in various cells of the human body. Recently, HYBID was found to over-express in the osteoarthritic chondrocytes... (Review)
Review
HYBID is a new hyaluronan-degrading enzyme and exists in various cells of the human body. Recently, HYBID was found to over-express in the osteoarthritic chondrocytes and fibroblast-like synoviocytes. According to these researches, high level of HYBID is significantly correlated with cartilage degeneration in joints and hyaluronic acid degradation in synovial fluid. In addition, HYBID can affect inflammatory cytokine secretion, cartilage and synovium fibrosis, synovial hyperplasia via multiple signaling pathways, thereby exacerbating osteoarthritis. Based on the existing research of HYBID in osteoarthritis, HYBID can break the metabolic balance of HA in joints through the degradation ability independent of HYALs/CD44 system and furthermore affect cartilage structure and mechanotransduction of chondrocytes. In particular, in addition to HYBID itself being able to trigger some signaling pathways, we believe that low-molecular-weight hyaluronan produced by excess degradation can also stimulate some disease-promoting signaling pathways by replacing high-molecular-weight hyaluronan in joints. The specific role of HYBID in osteoarthritis is gradually revealed, and the discovery of HYBID raises the new way to treat osteoarthritis. In this review, the expression and basic functions of HYBID in joints were summarized, and reveal potential role of HYBID as a key target in treatment for osteoarthritis.
Topics: Humans; Hyaluronic Acid; Mechanotransduction, Cellular; Osteoarthritis; Hyaluronoglucosaminidase; Disease Progression
PubMed: 37364478
DOI: 10.1016/j.biopha.2023.115043 -
Enhancement of the therapeutic efficacy of mesenchymal stem cell-derived exosomes in osteoarthritis.Cellular & Molecular Biology Letters Sep 2023Osteoarthritis (OA), a common joint disorder with articular cartilage degradation as the main pathological change, is the major source of pain and disability worldwide.... (Review)
Review
Osteoarthritis (OA), a common joint disorder with articular cartilage degradation as the main pathological change, is the major source of pain and disability worldwide. Despite current treatments, the overall treatment outcome is unsatisfactory. Thus, patients with severe OA often require joint replacement surgery. In recent years, mesenchymal stem cells (MSCs) have emerged as a promising therapeutic option for preclinical and clinical palliation of OA. MSC-derived exosomes (MSC-Exos) carrying bioactive molecules of the parental cells, including non-coding RNAs (ncRNAs) and proteins, have demonstrated a significant impact on the modulation of various physiological behaviors of cells in the joint cavity, making them promising candidates for cell-free therapy for OA. This review provides a comprehensive overview of the biosynthesis and composition of MSC-Exos and their mechanisms of action in OA. We also discussed the potential of MSC-Exos as a therapeutic tool for modulating intercellular communication in OA. Additionally, we explored bioengineering approaches to enhance MSC-Exos' therapeutic potential, which may help to overcome challenges and achieve clinically meaningful OA therapies.
Topics: Humans; Exosomes; Chondrocytes; Osteoarthritis; Cartilage, Articular; Mesenchymal Stem Cells
PubMed: 37770821
DOI: 10.1186/s11658-023-00485-2 -
Osteoarthritis and Cartilage Dec 2023We systematically reviewed the literature to identify comparative studies of core treatments (exercise, education, or weight management), adjunct treatments (e.g.... (Review)
Review
OBJECTIVE
We systematically reviewed the literature to identify comparative studies of core treatments (exercise, education, or weight management), adjunct treatments (e.g. electrotherapeutical modalities, bracing), or multimodal treatments (core plus other treatments), for treating osteoarthritis (OA) complaints, published between 1 March 2022 and 1 March 2023.
DESIGN
We searched three electronic databases for peer-reviewed comparative studies evaluating core treatments, adjunct treatments, or multimodal treatments for OA affecting any joint, in comparison to other OA treatments. Two authors independently screened records. Methodological quality was assessed using the Physiotherapy Evidence Database (PEDro) scale. A narrative synthesis focusing on pain and function outcomes was performed in studies with a mean sample size of at least 46 participants per treatment arm.
RESULTS
33 publications (28 studies), 82% with PEDro ratings of good or excellent, were eligible for narrative synthesis: 23 studies evaluated knee OA; one knee OA or chronic low back pain; two knee or hip OA; one hip OA only; and one thumb OA. No studies identified a dose, duration or type of exercise that resulted in better pain or function outcomes. Core treatments generally showed modest benefits compared to no or minimal intervention controls.
CONCLUSIONS
Rehabilitation research continues to be focused on the knee. Most studies are not adequately powered to assess pain efficacy. Further work is needed to better account for contextual effects, identify treatment responder characteristics, understand treatment mechanisms, and implement guideline care.
Topics: Humans; Osteoarthritis, Hip; Osteoarthritis, Knee; Physical Therapy Modalities; Pain; Exercise; Exercise Therapy
PubMed: 37673295
DOI: 10.1016/j.joca.2023.08.011 -
International Journal of Molecular... Jul 2023Osteoarthritis (OA) is progressive disease characterised by cartilage degradation, subchondral bone remodelling and inflammation of the synovium. The disease is... (Review)
Review
Osteoarthritis (OA) is progressive disease characterised by cartilage degradation, subchondral bone remodelling and inflammation of the synovium. The disease is associated with obesity, mechanical load and age. However, multiple pro-inflammatory immune mediators regulate the expression of metalloproteinases, which take part in cartilage degradation. Furthermore, genetic factors also contribute to OA susceptibility. Recent studies have highlighted that epigenetic mechanisms may regulate the expression of OA-associated genes. This review aims to present the mechanisms of OA pathogenesis and summarise current evidence regarding the role of genetics and epigenetics in this process.
Topics: Osteoarthritis; Epigenomics; Humans; Gene Expression Regulation; Genetic Predisposition to Disease; Inflammation; Animals
PubMed: 37511413
DOI: 10.3390/ijms241411655 -
Nutrients Oct 2023Osteoarthritis (OA) prevalence has increased 113% since 1990, and currently more than half a billion people worldwide are living with this slowly progressing,...
Osteoarthritis (OA) prevalence has increased 113% since 1990, and currently more than half a billion people worldwide are living with this slowly progressing, degenerative joint disease [...].
Topics: Humans; Osteoarthritis; Nutritional Status
PubMed: 37892417
DOI: 10.3390/nu15204336 -
International Immunopharmacology Aug 2023Osteoarthritis (OA) is a common disease of elderly individuals, with an unclear pathogenesis and limited treatment options to date. Inflammation occurs prominently in...
BACKGROUND
Osteoarthritis (OA) is a common disease of elderly individuals, with an unclear pathogenesis and limited treatment options to date. Inflammation occurs prominently in osteoarthritis, thereby making anti-inflammatory treatments promising in clinical outcomes. Therefore, it is of diagnostic and therapeutic significance to explore more inflammatory genes.
METHOD
In this study, appropriate datasets were first acquired through gene set enrichment analysis (GSEA), followed by inflammation-related genes through weighted gene coexpression network analysis (WGCNA). Two machine learning algorithms (random forest-RF and support vector machine-recursive feature elimination, SVM-RFE) were used to capture the hub genes. In addition, two genes negatively associated with inflammation and osteoarthritis were identified. Afterwards, these genes were verified through experiments and network pharmacology. Due to the association between inflammation and many diseases, the expression levels of the above genes in various inflammatory diseases were determined through literature and experiments.
RESULT
Two hub genes closely related to osteoarthritis and inflammation were obtained, namely, lysyl oxidase-like 1 (LOXL1) and pituitary tumour-transforming gene (PTTG1), which were shown to be highly expressed in osteoarthritis according to the literature and experiments. However, the expression levels of receptor expression-enhancing protein (REEP5) and cell division cycle protein 14B (CDC14B) remained unchanged in osteoarthritis. This finding was consistent with our verification from the literature and experiments that some genes were highly expressed in numerous inflammation-related diseases, while REEP5 and CDC14B were almost unchanged. Meanwhile, taking PTTG1 as an example, we found that inhibition of PTTG1 expression could suppress the expression of inflammatory factors and protect the extracellular matrix through the microtubule-associated protein kinase (MAPK) signalling pathway.
CONCLUSIONS
LOXL1 and PTTG1 were highly expressed in some inflammation-related diseases, while that of REEP5 and CDC14B were almost unchanged. PTTG1 may be a potential target for the treatment of osteoarthritis.
Topics: Aged; Humans; Inflammation; Osteoarthritis; Computational Biology; Gene Expression; Algorithms; Dual-Specificity Phosphatases
PubMed: 37301122
DOI: 10.1016/j.intimp.2023.110409