-
Journal of Orthopaedic Surgery and... Sep 2023Osteoarthritis (OA) is defined as a degenerative joint disease that can affect all tissues of the joint, including the articular cartilage, subchondral bone, ligaments... (Review)
Review
Osteoarthritis (OA) is defined as a degenerative joint disease that can affect all tissues of the joint, including the articular cartilage, subchondral bone, ligaments capsule, and synovial membrane. The conventional nonoperative treatments are ineffective for cartilage repair and induce only symptomatic relief. Platelet-rich plasma (PRP) is a platelet concentrate derived from autologous whole blood with a high concentration of platelets, which can exert anti-inflammatory and regenerative effects by releasing multiple growth factors and cytokines. Recent studies have shown that PRP exhibits clinical benefits in patients with OA. However, high operational and equipment requirements greatly limit the application of PRP to OA treatment. Past studies have indicated that high-concentration PRP growth factors and cytokines may be applied as a commercial replacement for PRP. We reviewed the relevant articles to summarize the feasibility and mechanisms of PRP-based growth factors in OA. The available evidence suggests that transforming growth factor-α and β, platelet-derived growth factors, epidermal growth factor, insulin-like growth factor-1, and connective tissue growth factors might benefit OA, while vascular endothelial growth factor, tumor necrosis factor-α, angiopoietin-1, and stromal cell derived factor-1α might induce negative effects on OA. The effects of fibroblast growth factor, hepatocyte growth factor, platelet factor 4, and keratinocyte growth factor on OA remain uncertain. Thus, it can be concluded that not all cytokines released by PRP are beneficial, although the therapeutic action of PRP has a valuable potential to improve.
Topics: Humans; Vascular Endothelial Growth Factor A; Epidermal Growth Factor; Chemokine CXCL12; Tumor Necrosis Factor-alpha; Osteoarthritis
PubMed: 37735688
DOI: 10.1186/s13018-023-04119-3 -
International Journal of Molecular... Jan 2024Osteoarthritis (OA) is a chronic joint disease characterized by articular cartilage degeneration, secondary bone hyperplasia, inadequate extracellular matrix synthesis... (Review)
Review
Osteoarthritis (OA) is a chronic joint disease characterized by articular cartilage degeneration, secondary bone hyperplasia, inadequate extracellular matrix synthesis and degeneration of articular cartilage. Mesenchymal stem cells (MSCs) can self‑renew and undergo multidirectional differentiation; they can differentiate into chondrocytes. Aging MSCs have a weakened ability to differentiate, and release various pro‑inflammatory cytokines, which may contribute to OA progression; the other mechanism contributing to OA is epigenetic regulation (for instance, DNA methylation, histone modification and regulation of non‑coding RNA). Owing to the self‑renewal and differentiation ability of MSCs, various MSC‑based exogenous cell therapies have been developed to treat OA. The efficacy of MSC‑based therapy is mainly attributed to cytokines, growth factors and the paracrine effect of exosomes. Recently, extensive studies have been conducted on MSC‑derived exosomes. Exosomes from MSCs can deliver a variety of DNA, RNA, proteins and lipids, thereby facilitating MSC migration and cartilage repair. Therefore, MSC‑derived exosomes are considered a promising therapy for OA. The present review summarized the association between MSC aging and OA in terms of genetics and epigenetics, and characteristics of MSC‑derived exosomes, and the mechanism to alleviate OA cartilage damage.
Topics: Humans; Epigenesis, Genetic; Osteoarthritis; Cell Differentiation; Cartilage, Articular; Mesenchymal Stem Cells; Cytokines; Exosomes; Chondrocytes
PubMed: 37937669
DOI: 10.3892/ijmm.2023.5326 -
PloS One 2023Numerous observational studies have shown that obesity (OB) is a significant risk factor in the occurrence and progression of osteoarthritis (OA), but the underlying...
Numerous observational studies have shown that obesity (OB) is a significant risk factor in the occurrence and progression of osteoarthritis (OA), but the underlying molecular mechanism between them remains unclear. The study aimed to identify the key genes and pathogeneses for OA with OB. We obtained two OA and two OB datasets from the gene expression omnibus (GEO) database. First, the identification of differentially expressed genes (DEGs), weighted gene co-expression network analysis (WGCNA), and machine learning algorithms were used to identify key genes for diagnosing OA with OB, and then the nomogram and receiver operating characteristic (ROC) curve were conducted to assess the diagnostic value of key genes. Second, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to explore the pathogenesis of OA with OB. Third, CIBERSORT was created to investigate immunocyte dysregulation in OA and OB. In this study, two genes (SOD2, ZNF24) were finally identified as key genes for OA with OB. These two key genes had high diagnostic values via nomogram and ROC curve calculation. Additionally, functional analysis emphasized that oxidative stress and inflammation response were shared pathogenesis of OB and AD. Finally, in OA and OB, immune infiltration analysis showed that SOD2 closely correlated to M2 macrophages, regulatory T cells, and CD8 T cells, and ZNF24 correlated to regulatory T cells. Overall, our findings might be new biomarkers or potential therapeutic targets for OA and OB comorbidity.
Topics: Humans; Obesity; Osteoarthritis; Risk Factors; Algorithms; Computational Biology
PubMed: 38127891
DOI: 10.1371/journal.pone.0296033 -
Experimental & Molecular Medicine Dec 2023Osteoarthritis (OA) is a degenerative joint disease. While it is classically characterized by articular cartilage destruction, OA affects all tissues in the joints and...
Osteoarthritis (OA) is a degenerative joint disease. While it is classically characterized by articular cartilage destruction, OA affects all tissues in the joints and is thus also accompanied by local inflammation, subchondral bone changes, and persistent pain. However, our understanding of the underlying subchondral bone dynamics during OA progression is poor. Here, we demonstrate the contribution of immunoglobulin superfamily 11 (IgSF11) to OA subchondral bone remodeling by using a murine model. In particular, IgSF11 was quickly expressed by differentiating osteoclasts and upregulated in subchondral bone soon after destabilization-of-the-medial-meniscus (DMM)-induced OA. In mice, IgSF11 deficiency not only suppressed subchondral bone changes in OA but also blocked cartilage destruction. The IgSF11-expressing cells in OA subchondral bone were found to be involved in osteoclast maturation and bone resorption and colocalized with receptor-activator of nuclear-factor κ-B (RANK), the key osteoclast differentiation factor. Thus, our study shows that blocking early subchondral bone changes in OA can ameliorate articular cartilage destruction in OA.
Topics: Animals; Mice; Bone and Bones; Bone Resorption; Cartilage, Articular; Disease Models, Animal; Osteoarthritis; Osteoclasts
PubMed: 38036734
DOI: 10.1038/s12276-023-01126-6 -
Current Rheumatology Reports Dec 2023This narrative review article comprehensively explains the pathophysiology of osteoarthritis (OA) pain perception, how the gut microbiota is correlated with it, possible... (Review)
Review
PURPOSE OF REVIEW
This narrative review article comprehensively explains the pathophysiology of osteoarthritis (OA) pain perception, how the gut microbiota is correlated with it, possible molecular pathways involved in probiotics-mediated OA pain reduction, limitations in the current research approaches, and future perspectives.
RECENT FINDINGS
The initiation and progression of OA, including the development of chronic pain, is intricately associated with activation of the innate immune system and subsequent inflammatory responses. Trauma, lifestyle (e.g., obesity and metabolic disease), and chronic antibiotic treatment can disrupt commensal homeostasis of the human microbiome, thereby affecting intestinal integrity and promoting leakage of bacterial endotoxins and metabolites such as lipopolysaccharides (LPS) into circulation. Increased level of LPS is associated with knee osteophyte severity and joint pain. Both preclinical and clinical studies strongly suggest that probiotics may benefit patients with OA pain through positive gut microbiota modulation and attenuating low-grade inflammation via multiple pathways. Patent data also suggests increased interest in the development of new innovations that involve probiotic use for reducing OA and joint pain. Recent data suggest that probiotics are attracting more and more attention for OA pain management. The advancement of knowledge in this area may pave the way for developing different probiotic strains that can be used to support joint health, improve treatment outcomes in OA, and reduce the huge impact of the disease on healthcare systems worldwide.
Topics: Humans; Lipopolysaccharides; Osteoarthritis; Pain; Probiotics; Arthralgia
PubMed: 37656392
DOI: 10.1007/s11926-023-01108-7 -
Journal of Nanobiotechnology Oct 2023Osteoarthritis (OA) is a prevalent joint disease that affects all the tissues within the joint and currently lacks disease-modifying treatments in clinical practice....
Osteoarthritis (OA) is a prevalent joint disease that affects all the tissues within the joint and currently lacks disease-modifying treatments in clinical practice. Despite the potential of rapamycin for OA disease alleviation, its clinical application is hindered by the challenge of achieving therapeutic concentrations, which necessitates multiple injections per week. To address this issue, rapamycin was loaded into poly(lactic-co-glycolic acid) nanoparticles (RNPs), which are nontoxic, have a high encapsulation efficiency and exhibit sustained release properties for OA treatment. The RNPs were found to promote chondrogenic differentiation of ATDC5 cells and prevent senescence caused by oxidative stress in primary mouse articular chondrocytes. Moreover, RNPs were capable to alleviate metabolism homeostatic imbalance of primary mouse articular chondrocytes in both monolayer and 3D cultures under inflammatory or oxidative stress. In the mouse destabilization of the medial meniscus (DMM) model, intra-articular injection of RNPs effectively mitigated joint cartilage destruction, osteophyte formation, chondrocytes hypertrophy, synovial inflammation, and pain. Our study demonstrates the feasibility of using RNPs as a potential clinically translational therapy to prevent the progression of post-traumatic OA.
Topics: Mice; Animals; Sirolimus; Cartilage, Articular; Osteoarthritis; Disease Models, Animal; Nanoparticles
PubMed: 37794470
DOI: 10.1186/s12951-023-02118-4 -
Medicine Nov 2023Extracorporeal shockwave therapy (ESWT) has been widely used for various musculoskeletal disorders, including knee osteoarthritis (OA), and has been shown in several... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Extracorporeal shockwave therapy (ESWT) has been widely used for various musculoskeletal disorders, including knee osteoarthritis (OA), and has been shown in several studies to be a safe treatment. Although some studies have confirmed the pain-relieving effect of ESWT for knee OA, research on objectivity for structural changes in knee OA is lacking. The aim of this study was to evaluate the ESWT treatment mechanisms in patients with knee OA by means of clinical symptoms and ultrasound techniques as objective measures.
METHODS
Eighteen patients with mild knee OA were enrolled and randomized to 1 of 2 treatment groups: active or sham. Patients in the experimental group received 0.05 mJ/mm² total energy with 1000 pulses weekly for 3 weeks. We then assessed them before, immediately after, and 1-month after the last treatment using the following measurements: pain on a visual analog scale, Western Ontario and McMaster Universities Osteoarthritis Index, Lequesne index, knee joint range of motion, and ultrasonographic features (articular cartilage thickness, Doppler activity, and joint effusion height).
RESULTS
All 18 patients completed the 3 treatment sessions without any complication. Both the experimental and control groups improved in terms of OA symptoms, as measured by the visual analog scale, Western Ontario and McMaster Universities Osteoarthritis Index score, and Lequesne index (P < .05). The height of the suprapatellar effusion decreased with time course in the experimental group (P < .05) and showed significant differences with control group at 1-month follow-up (P < .05). The experimental group showed an increase in knee flexion range of motion and Doppler activity immediately following the last treatment session (P < .05), but the effect was not sustained at the 1-month follow-up.
CONCLUSIONS
Although the therapeutic activity itself could improve OA symptoms, objective improvements were only observed after ESWT. Suprapatellar effusion height was reduced after ESWT and the effect was maintained after 1-month. Our results suggest that ESWT may be effective in reducing suprapatellar effusion and improving symptoms in mild knee OA. However, studies with a larger sample size are required.
Topics: Humans; Osteoarthritis, Knee; Pilot Projects; Extracorporeal Shockwave Therapy; Knee Joint; Pain; Treatment Outcome
PubMed: 37986308
DOI: 10.1097/MD.0000000000036117 -
Aging Cell Nov 2023Senolytic drugs are designed to selectively clear senescent cells (SnCs) that accumulate with injury or aging. In a mouse model of osteoarthritis (OA), senolysis yields...
Senolytic drugs are designed to selectively clear senescent cells (SnCs) that accumulate with injury or aging. In a mouse model of osteoarthritis (OA), senolysis yields a pro-regenerative response, but the therapeutic benefit is reduced in aged mice. Increased oxidative stress is a hallmark of advanced age. Therefore, here we investigate whether senolytic treatment differentially affects joint oxidative load in young and aged animals. We find that senolysis by a p53/MDM2 interaction inhibitor, UBX0101, reduces protein oxidative modification in the aged arthritic knee joint. Mass spectrometry coupled with protein interaction network analysis and biophysical stability prediction of extracted joint proteins revealed divergent responses to senolysis between young and aged animals, broadly suggesting that knee regeneration and cellular stress programs are contrarily poised to respond as a function of age. These opposing responses include differing signatures of protein-by-protein oxidative modification and abundance change, disparate quantitative trends in modified protein network centrality, and contrasting patterns of oxidation-induced folding free energy perturbation between young and old. We develop a composite sensitivity score to identify specific key proteins in the proteomes of aged osteoarthritic joints, thereby nominating prospective therapeutic targets to complement senolytics.
Topics: Male; Mice; Animals; Senotherapeutics; Disease Models, Animal; Oxidative Stress; Aging; Osteoarthritis; Cellular Senescence
PubMed: 37749958
DOI: 10.1111/acel.13979 -
Expert Reviews in Molecular Medicine Apr 2024Osteoarthritis (OA) commonly affects the knee and hip joints and accounts for 19.3% of disability-adjusted life years and years lived with disability worldwide (Refs ,... (Review)
Review
Osteoarthritis (OA) commonly affects the knee and hip joints and accounts for 19.3% of disability-adjusted life years and years lived with disability worldwide (Refs , ). Early management is important in order to avoid disability uphold quality of life (Ref. ). However, a lack of awareness of subclinical and early symptomatic stages of OA often hampers early management (Ref. ). Moreover, late diagnosis of OA among those with severe disease, at a stage when OA management becomes more complicated is common (Refs , , , ). Established risk factors for the development and progression of OA include increasing age, female, history of trauma and obesity (Ref. ). Recent studies have also drawn a link between OA and metabolic syndrome, which is characterized by insulin resistance, dyslipidaemia and hypertension (Refs , ).
Topics: Humans; Female; Osteoarthritis, Knee; Quality of Life; Osteoarthritis, Hip; Diabetes Mellitus; Biomarkers
PubMed: 38606593
DOI: 10.1017/erm.2024.7 -
Biomedicine & Pharmacotherapy =... Oct 2023Osteoarthritis (OA) is a common debilitating degenerative disease of the elderly. We aimed to study the therapeutic effects of combining curcumin and swimming in...
Osteoarthritis (OA) is a common debilitating degenerative disease of the elderly. We aimed to study the therapeutic effects of combining curcumin and swimming in monosodium iodoacetate (MIA)-induced OA in a rat model. The rats were divided into 5 groups (n = 9). Group 1 received saline and served as a control group. Groups 2-5 were injected intra-articularly in the right knee with 100 μL MIA. One week later, groups 3 and 5 were started on daily swimming sessions that gradually increased to 20-mins per session, and for groups 4 and 5, oral curcumin was administered at a dose of 200 mg/kg for 4 weeks. The combination therapy (curcumin + swimming) showed the most effective results in alleviating pain and joint stiffness as well as improving histological and radiological osteoarthritis manifestations in the knee joints. The combination modality also reduced serum C-reactive protein and tissue cartilage oligomeric matrix protein levels. Mechanistically, rats received dual treatment exhibited restoration of miR-130a and HDAC3 expression. The dual treatment also upregulated PPAR-γ alongside downregulation of NF-κB and its inflammatory cytokine targets TNF-α and IL-1β. Additionally, there was downregulation of MMP1 and MMP13 in the treated rats. In conclusion, our data showed that there is a therapeutic potential for combining curcumin with swimming in OA, which is attributed, at least in part, to the modulation of miR-130a/HDAC3/PPAR-γ signaling axis.
Topics: Rats; Animals; Curcumin; Peroxisome Proliferator-Activated Receptors; Swimming; Cartilage, Articular; Disease Models, Animal; Osteoarthritis; Iodoacetic Acid; MicroRNAs
PubMed: 37573656
DOI: 10.1016/j.biopha.2023.115309