Osteoarthritis Research Research Articles

Foot osteoarthritis research: A bibliometric analysis.

To conduct a bibliographic analysis of English language, non-surgical research pertaining to foot osteoarthritis (OA). The Scopus® database search was conducted to identify all non-surgical foot OA articles published in English up until December 2023. Bibliometric analysis was performed using an open-source tool based on the R language. Citations, journals, authors, institutions, and countries were described. Publications were manually categorised according to research type and funding source. The search strategy yielded 121 eligible articles, which received a total of 4531 citations and were published by 372 authors in 55 journals. The highest publication output occurred in the past decade. The most frequent journals were Arthritis Care & Research, Osteoarthritis and Cartilage, Journal of the American Podiatric Medical Association, Annals of the Rheumatic Diseases, Foot & Ankle International and Journal of Foot and Ankle Research. The most published institutions were Keele University, La Trobe University, the University of Leeds, the University of Melbourne and the University of North Carolina. Of the 106 articles that could be classified, most were focused on aetiology (n=52, 49%), followed by evaluation of treatments and therapeutic interventions (n=28, 26%), detection, screening and diagnosis (n=17, 16%), health and social care services research (n=6, 6%) and underpinning research (3, 3%). Fifty-one articles (42%) reported no research funding. Foot OA research has increased significantly in the past decade. There is a need, however, to improve our understanding of the condition and to address the relatively small number of clinical trials that have been conducted.

Characterization of a chemically induced osteoarthritis model in zebrafish

Osteoarthritis (OA) is characterized by the progressive degeneration of the synovial joint, leading to irreversible damage to articular cartilage and subchondral bone. While animal models have advanced our understanding of OA, numerous unresolved issues still remain. The zebrafish, known for its transparent body, rapid developmental, and impressive regenerative capabilities, offers substantial potential for osteoarthritis research. This study seeks to establish a new OA model utilizing the zebrafish jaw joint, acting as a supplement to traditional animal models. In the future, this model could serve as a valuable platform for delving deeper into the mechanisms of this disease, as well as for advancing drug discovery and therapeutic interventions. Leveraging the skeletal structure of zebrafish, we targeted the largest jaw joint for our research. A custom fixation device was crafted, and a microinjection system was utilized to inject mono-iodoacetate (MIA) or collagenase type II (CTII) into the joint cavity of zebrafish. Subsequent analyses included histological staining, immunohistochemistry, OA research society international (OARSI) scoring, and real-time in vivo imaging were performed at 7, 14, and 28 days post injection. Our results effectively demonstrated the presence of synovial inflammation and cartilage damage within the zebrafish mandible, affirming the feasibility of inducing OA in zebrafish. In conclusion, the local injection of chemical agents into the joint cavity of zebrafish effectively induced the occurrence of OA. Establishing the zebrafish OA model enhances the array of animal models available for OA research. Moreover, zebrafish present distinct advantages, including robust regenerative abilities, genetic editing simplicity, and efficient drug screening. Consequently, this offers a fresh avenue for investigating the pathogenesis, prevention, and potential therapeutic approaches for human OA.

Additive effects of curcumin and glucosamine on knee function, cartilage protection, and subchondral bone preservation in a post-traumatic osteoarthritis rat model

Background: Osteoarthritis (OA) increasingly become a global public health concern. Curcumin and glucosamine, both widely used as dietary supplements for OA, have shown distinct therapeutic effects. However, curcumin’s low bioavailability and the debated efficacy of glucosamine limit their broader clinical use. Objective: Investigate the combined effects of curcumin and glucosamine on knee function, subchondral bone preservation, and cartilage protection in post-traumatic OA rat. Methods: Post-traumatic OA was induced in Lewis rats through medial meniscus transection (MMT) surgery. Rats were treated for 8 weeks with curcumin phospholipid liposome (C, 120 mg/kg/day), glucosamine (G, 190 mg/kg/day), or a combination of both (CG, C: G=1:3, 63/190 mg/kg/day). Knee width was measured weekly, and weight-bearing was assessed twice weekly. Subchondral bone and cartilage changes were analyzed using micro-CT, toluidine blue staining, and the OARSI (Osteoarthritis Research Society International) score. Collagen II expression in cartilage was evaluated by immunohistochemistry. Results: Curcumin phospholipid liposomes significantly reduced joint swelling by up to 4.1% (P<0.001) and improved weight-bearing force by 24.2% at week 2 (P<0.01) and 14.9% at week 8 (P<0.05) in comparison with the MMT group. Analysis of Micro-CT indicated an increase in bone volume (11.6%) and bone mineral content (13.0%) (P<0.05). Histological analysis showed a 28.8% reduction in OARSI scores (P<0.01) and a 53.1% increase in collagen II expression (P<0.005). Glucosamine treatment reduced joint swelling by up to 5.7% (P<0.0001), improved weight-bearing by 31.6% (P<0.001) at week 2, and significantly increased bone volume (30.4%) and bone mineral content (29.9%) (P<0.05). The combined treatment further reduced swelling by up to 6.6% (P<0.0001) and improved the R/L weight-bearing ratio by 24.7% (P<0.0001) at week 8. It also enhanced bone volume (28.6%), bone mineral content (29.7%, and anisotropy degree (59.3%) (P< 0.05). Additionally, the combination therapy decreased OARSI scores by 27.1% (P<0.01) and enhanced the expression of collagen II by 54.2% (P<0.005), indicating enhanced cartilage and subchondral bone protection. Conclusion: Curcumin showed superior protection for cartilage, while glucosamine mainly benefited subchondral bone. Combined treatment demonstrated additive effects, improving both knee structure and physical function in OA, offering enhanced pain relief, anti-inflammatory action, and joint preservation.

Recent advances in osteoarthritis research: A review of treatment strategies, mechanistic insights, and acupuncture.

Osteoarthritis (OA) is a chronic joint condition affecting millions worldwide, characterized by the gradual degeneration of joint cartilage, leading to pain, stiffness, and functional impairment. Although the pathogenesis of OA is not fully understood, the roles of inflammation, metabolic dysregulation, and biomechanical stress are increasingly recognized. Current treatments, including pharmacotherapy, physical therapy, and surgical interventions, aim to alleviate symptoms and improve quality of life, yet they face limitations and challenges. In recent years, researchers have explored a variety of new treatment strategies, such as molecular targeted therapy, biologic treatments, regenerative medicine, and lifestyle modifications, aiming to directly address the root causes and complex mechanisms of OA. This review aims to summarize the latest research advancements to provide fresh perspectives for clinical treatment and lay the foundation for future research and development of treatment strategies for OA.

A genome-wide association study identifies genetic variants associated with hip pain in the UK Biobank cohort (N = 221,127)

Hip pain is a common musculoskeletal complaint that leads many people to seek medical attention. We conducted a primary genome-wide association study (GWAS) on the hip pain phenotype within the UK Biobank cohort. Sex-stratified GWAS analysis approach was also performed to explore sex specific variants associated with hip pain. We found seven different loci associated with hip pain at GWAS significance level, with the most significant single nucleotide polymorphism (SNP) being rs77641763 within the EXD3 (p value = 2.20 × 10–13). We utilized summary statistics from the FinnGen cohort and a previous GWAS meta-analysis on hip osteoarthritis as replication cohorts. Four loci (rs509345, rs73581564, rs9597759, rs2018384) were replicated with a p value less than 0.05. Sex-stratified GWAS analyses revealed a unique locus within the CUL1 gene (rs4726995, p = 2.56 × 10–9) in males, and three unique loci in females: rs1651359966 on chromosome 7 (p = 1.15 × 10–8), rs552965738 on chromosome 9 (p = 2.72 × 10–8), and rs1978969 on chromosome 13 (p = 2.87 × 10–9). This study has identified seven genetic loci associated with hip pain. Sex-stratified analysis also revealed sex specific variants associated with hip pain in males and females. This study has provided a foundation for advancing research of hip pain and hip osteoarthritis.

In clinical hand osteoarthritis research, self-reported pain questionnaires do not reflect the patient experience.

Pain in hand osteoarthritis (OA) is evaluated with repeated pain questionnaires. It is unclear whether these questionnaires adequately capture changes in pain recalled by patients. This study investigated whether changes on pain questionnaires (real-time evaluation) correspond to recalled pain. Data from hand OA patients from the HOSTAS cohort (four one-yearly) and HOPE trial (one six-week interval) were used. Pain was measured with the Australian/Canadian hand Osteoarthritis Index (AUSCAN, range 0-20) and a recall question (how is the pain compared with your last visit). Changes in AUSCAN pain were categorized into improved (≤-1), stable or worsened pain (≥1) and compared with the recall question using Cohen's kappa and percentage agreement. We determined concordance between measurement methods, and investigated associations of mental wellbeing and illness perceptions with concordance using GEE. Of 708 intervals from HOSTAS (307 patients, 82% women, mean age 61.0 years, mean AUSCAN 9.1), AUSCAN changes and recall were concordant in 42% (Cohen's kappa 0.13). There was concordance in 47% of 86 intervals (Cohen's kappa 0.14) from the HOPE trial (86 patients, 80% women, mean age 63.5, mean AUSCAN 10.7). The most frequent recall answer was worsened pain in the HOSTAS (60%), improved pain in the HOPE trial (76%). In both studies, AUSCAN pain most frequently improved. Depression and anxiety showed no association with concordance. Changes in repeatedly measured AUSCAN pain often differ from the recalled course of pain over the same period. This has profound implications for evaluating patient reported pain in clinical trials.

Regulation of fibroblast phenotype in osteoarthritis using CDKN1A-loaded copper sulfide nanoparticles delivered by mesenchymal stem cells.

This study aimed to investigate the regulation of fibroblast phenotypes by mesenchymal stem cells (MSCs) delivering copper sulfide (CuS) nanoparticles (NPs) loaded with CDKN1A plasmids and their role in cartilage repair during osteoarthritis (OA). Single-cell RNA sequencing data from the GEO database were analyzed to identify subpopulations within the OA immune microenvironment. Quality control, filtering, principal component analysis (PCA) dimensionality reduction, and tSNE clustering were performed to obtain detailed cell subtypes. Pseudotime analysis was used to understand the developmental trajectory of fibroblasts, and GO/KEGG enrichment analyses highlighted biological processes related to fibroblast function. Transcriptomic data and WGCNA identified CDKN1A as a key regulatory gene. A biomimetic CuS@CDKN1A nanosystem was constructed and loaded into MSCs to create MSCs@CuS@CDKN1A. The characterization of this system confirmed its efficient cellular uptake by fibroblasts. In vitro experiments demonstrated that MSCs@CuS@CDKN1A significantly modulated fibroblast phenotypes and improved the structure, proliferation, reduced apoptosis, and enhanced migration of IL-1β-stimulated chondrocytes. In vivo, an OA mouse model was treated with intra-articular injections of MSCs@CuS@CDKN1A. Micro-CT scans revealed a significant reduction in osteophyte formation and improved joint space compared with control groups. Histological analysis, including H&E, Safranin O-Fast Green, and toluidine blue staining, confirmed improved cartilage integrity, whereas the International Osteoarthritis Research Society (OARSI) scoring indicated reduced disease severity. Immunofluorescence showed upregulated CDKN1A expression, decreased MMP13, and reduced α-SMA expression in fibroblast subtypes. Major organs exhibited no signs of toxicity, confirming the biocompatibility and safety of the treatment. These findings suggest that MSCs@CuS@CDKN1A can effectively regulate fibroblast activity and promote cartilage repair, providing a promising therapeutic strategy for OA treatment.NEW & NOTEWORTHY This study introduces MSCs@CuS@CDKN1A, a nanoengineered MSC platform that targets fibroblast phenotypes in osteoarthritis (OA). By modulating CDKN1A expression, this innovative approach not only enhances cartilage repair but also effectively mitigates fibroblast-driven inflammation, marking a significant advancement in OA therapeutics with demonstrated efficacy and biocompatibility.

Current Research Trends and Advances in Osteoarthritis: A Bibliometric Study

Background: With the aging of the population and the rise in obesity and injury rates, the prevalence of osteoarthritis (OA) is increasing annually. Therefore, it is necessary to study experimental OA models. Methods: From January 1, 2000 to November 25, 2023, articles on the selection of experimental OA models from the Web of Science Core Collection (WOSCC) were collected. CiteSpace was used to analyze countries or regions, institutions, authors, bursting keywords, and references. Co-authorship, co-journal, and keyword co-occurrence visual analyses were performed using VOSviewer. Results: An analysis of 3,206 articles found that the annual volume of articles showed a rapid growth trend. The United States leads in terms of number of publications (1,039), total citations (29,844), h-index (77), and intermediary centrality (0.24), showing the journal with the most articles on Osteoarthritis and Cartilage. The emerging keywords stem cell, cartilage repair, and oxidative stress from 2019 to 2023 reflect the current study hotspots. Conclusion: This study comprehensively summarizes the research progress of OA model selection and evaluation criteria using bibliometric analysis, and provides a valuable reference for further establishing OA standard models, evaluation criteria, and researchers in this field.

Intra-articular Injections of CXCR4-Overexpressing Human Cartilage-Derived Progenitor Cells Improve Meniscus Healing and Protect Against Posttraumatic Osteoarthritis in Immunocompetent Rabbits.

Meniscal injuries that fail to heal instigate catabolic changes in the knee's microenvironment, posing a high risk for developing posttraumatic osteoarthritis (PTOA). Previous research has suggested that human cartilage-derived progenitor cells (hCPCs) can stimulate meniscal repair in a manner that depends on stromal cell-derived factor 1 (SDF-1) pathway activity. Overexpressing the SDF-1 receptor CXCR4 in hCPCs will increase cell trafficking and further improve the repair efficacy of meniscal injuries. Controlled laboratory study. hCPCs were genetically modified to overexpress CXCR4 (CXCR4-overexpressing [OE] hCPCs) using lentivirus. In vitro characterization was performed using cell viability assay, cell migration assay, and immunoblotting. These cells were then used to treat a meniscal injury in rabbits. A medial meniscal tear was surgically created in the right knees of New Zealand White rabbits, followed by 2 intra-articular injections (5.0 × 106 cells each) of either CXCR4-OE hCPCs, wild-type hCPCs, or saline alone. A histological assessment of menisci and cartilage was performed using safranin O/fast green staining. Joints were assessed for PTOA changes using the modified Osteoarthritis Research Society International scoring system. Fluorescence imaging and DNA analysis were performed to examine tissue for human cells. SDF-1 inhibited NF-κB and ERK pathways in both wild-type and CXCR4-OE hCPCs. CXCR4 overexpression increased hCPC trafficking toward sources of SDF-1, including injured meniscal fibrocartilage and an SDF-1-presoaked collagen scaffold. Intra-articular injections of CXCR4-OE hCPCs significantly improved meniscus healing, as evidenced by the complete absence of tears in 5 of 6 (83%) animals that received CXCR4-OE hCPCs compared with only 3 of 6 (50%) wild-type hCPC-treated animals and 2 of 6 (33%) animals in the saline control group. CXCR4-OE hCPC-treated animals also showed significantly less erosion in their knee cartilage compared with control animals. Overall, CXCR4 overexpression inhibited catabolic pathway signaling in hCPCs and increased cell migration. Evidence suggests that intra-articular injections of these cells into the injured knee allow them to home in on sites of fibrocartilage injuries and ultimately result in meniscal tear healing and PTOA inhibition in immunocompetent animals. This study demonstrated that cartilage progenitors with elevated CXCR4 expression have the potential to be a potent therapeutic tool for stimulating meniscal tear healing.

Exploring bovine three-dimensional chondrocyte culture models in osteoarthritis research: A systematic review

Background: The use of different animal species for chondrocyte culture has been employed to investigate the diseases that affect cartilage, including osteoarthritis. Bovine cartilage and chondrocytes can be used to establish three-dimensional cell cultures, which offer a more dependable in vitro model when compared to conventional monolayer cultures. However, bovine chondrocytes in three-dimensional cultures have not been widely implemented, losing a potential source of mammal tissue that could prove valuable for preclinical studies on osteoarthritis. Objective: The objective of this study was to conduct a comprehensive review of the existing scientific literature that employs three-dimensional cultures of bovine cartilage to investigate osteoarthritis. Methods: A systematic search was performed using the electronic databases PubMed and Scopus, to identify clinical studies using 3D cell culture for osteoarthritis. Search terms included: ´3D culture’, ‘3D cell culture’, ‘bovine cartilage’ and ‘chondrocyte’. A total of 59 articles were gathered, and after screening, 12 articles were included in the final analysis. Risk of bias assessment was conducted categorizing each of the studies as having a 'low,' 'medium,' or 'high' risk of bias. Results: Analysis of the articles included in this review highlighted the increased variability in harvesting sites involving carpal, metacarpal, and knee joints, as well as variation in culture methods utilizing cell passages ranging from passage zero to passage nine. Moreover, medium, and high risk of bias were detected in all the articles probably due to challenges in randomization and blinding of the studies. In summary, this review critically examines three-dimensional cell culture for the investigation of cartilage disorders, with a particular emphasis on bovine cartilage. Conclusions: Future studies should include consistent methods across the in vitro phase of the study, such as uniform harvest sites, as well as using early chondrocyte passages to preserve cellular phenotype. Furthermore, comparison of relevant translational models should include age-matched conditions to avoid further confounding factors.

Exploring the Analgesic Effect of Acupuncture on Knee Osteoarthritis Based on MLT/cAMP/PKA/CREB Signaling Pathway.

Acupuncture is an effective treatment for knee osteoarthritis (KOA), reducing pain and improving function. While melatonin (MLT) has notable pain relief benefits, the analgesic mechanism of acupuncture in KOA and its relationship with melatonin are still unknown. This study aims to explore this mechanism. In this work, the KOA rabbit model was constructed using the traditional Hulth method, and the therapeutic effect was assessed by the Lequesne MG score and Pain assessment by hot plate test. The pathological alterations of cartilage tissue were observed using hematoxylin and eosin (H&E) staining, Safranin O-fast green and MASSON staining to observe the pathological changes in cartilage tissue, and the efficacy was evaluated according to the principles of Mankin score and Osteoarthritis Research Society International (OARSI) score. Meanwhile, MLT in serum, cyclic adenosine monophosphate (cAMP) in cartilage, and matrix metalloproteinase-3 (MMP-3) in joint fluid were detected by enzyme-linked immunosorbent assay. In addition, the expression of aromatic L-amino acid N-acetyltransferase (AANAT), melatonin receptor 1 (MT1) and 2 (MT2) mRNAs in cartilage was determined by real-time quantitative reverse transcription-polymerase chain reaction, and the levels of proteins related to PKA/CREB signaling pathway were detected by Western blotting. Based on the results of Lequesne MG score and Pain assessment by hot plate test experimental data, the treatment group presented significant improvements in knee pain and overall function relative to OA (Osteoarthritis) group. Besides, according to results of histologic staining, Mankin and OARSI scores, articular cartilage degeneration of treatment group remarkably improved. In addition, acupuncture significantly reduced the expression of the inflammatory factor MMP-3 in knee joint fluid and significantly increased the levels of MLT, AANAT, MT1, MT2, cAMP, PKA and CREB. By regulating sympathetic excitability, acupuncture may activate the MLT/cAMP/PKA/CREB signaling pathway, decrease inflammatory factor expression and slow down degradation of articular cartilage, resulting in the relief of knee pain.

Ketogenic Diet-Associated Worsening of Osteoarthritis Histologic Secerity, Increased Pain Sensitivity and Gut Microbiome Dysbiosis in Mice.

Dietary interventions are a potentially powerful treatment option for knee osteoarthritis (OA). The objective of this study was to evaluate a well-formulated ketogenic diet (KD) in the context of knee OA histology and pain using the destabilization of the medial meniscus (DMM) mouse model and correlate with gut microbiome and systemic cytokine levels. Adult male mice underwent unilateral DMM or sham surgery and were then fed eight weeks of KD or chow. At baseline and every two weeks, mechanical allodynia of the operated and contralateral knees was assessed via analgesiometry. Knee joints were collected for histology, gut microbiome analysis was performed on cecal material via 16S sequencing, and serum cytokines were analyzed via Bio-Plex assay. KD mice had worse histopathologic OA after DMM (mean ± SEM Osteoarthritis Research Society International score: KD-DMM: 4.0 ± 0.5 vs chow-DMM: 2.7 ± 0.08; P=0.02). KD mice had increased mechanical allodynia postsurgery (P=0.005 in mixed-effects model). The gut microbiome changed substantially with KD: 59 clades were altered by KD in DMM and 39 by KD in sham (36 were shared, 25 overlapped with previous murine OA studies). Several clades were correlated on an individual-mouse level with both histology and allodynia (eg, Lactobacillus histology P=0.004, allodynia P=1 × 10-4). Serum analysis showed four cytokines increased with KD (interleukin [IL]-1β, IL-2, IL-3, and IL-13). KD started immediately after OA induction via DMM is associated with worsened histologic outcomes. KD also worsens mechanical allodynia after either DMM or sham surgery. KD induces significant gut microbiome dysbiosis in clades previously associated with murine OA.

M13, an anthraquinone compound isolated from Morinda officinalis alleviates the progression of the osteoarthritis via the regulation of STAT3.

Osteoarthritis (OA) is characterized by the progressive deterioration of articular cartilage, leading to joint pain and functional impairment. OA severely impacts quality of life and presents a substantial societal burden. Currently, effective treatment options remain limited. Morinda officinalis (MO), a traditional Chinese herb, is commonly used to treat rheumatoid arthritis and alleviate joint pain. M13, an anthraquinone extracted from MO, has shown significant anti-inflammatory properties, making it a promising candidate for the treatment of OA. However, its role in inhibiting OA progression and the mechanisms involved remain poorly understood. The objective of this study is to examine the impact of M13 on osteoarthritis and uncover the mechanisms. The effects of M13 on OA were assessed using TNF-α induced chondrocyte models and mice with destabilization of the medial meniscus (DMM). Celecoxib was used as a positive control. We evaluated the expression of factors related to chondrocyte degeneration and inflammation through qRT-PCR, immunoblotting, and immunofluorescence. Chondrocyte viability was measured using CCK-8 assays, EdU staining, and flow cytometry. Molecular docking, molecular dynamics simulations and isothermal titration calorimetry (ITC) were performed to evaluate the binding efficacy of target proteins. Additionally, the therapeutic effects of M13 in OA mice were confirmed through in vivo experiments. In primary murine chondrocytes, M13 rescued TNF-α-induced matrix degradation and loss of vitality while suppressing ROS generation. Mechanistically, STAT3 was identified as a target protein of M13, through which M13 mitigated OA by inhibiting the STAT3 signaling pathway. Further in vivo experiments demonstrated that M13 reduced the scores of the Osteoarthritis Research Society International (OARSI), alleviating cartilage impairment. M13 enhanced levels of collagen II and aggrecan in cartilage tissue while decreasing the amounts of cartilage-degrading proteins ADAMTS-5 and MMP13. This is the first study to validate that M13 mitigates the inflammation and damage in cartilage tissue by blocking the STAT3 signaling pathway. These findings hold promise for enhancing innovative clinical interventions targeting OA.

A click chemistry-based biorthogonal approach for the detection and identification of protein lysine malonylation for osteoarthritis research.

Lysine malonylation is a post-translational modification where a malonyl group, characterized by a negatively charged carboxylate, is covalently attached to the ε-amino side chain of lysine, influencing protein structure and function. Our laboratory identified Mak upregulation in cartilage under aging and obesity, contributing to osteoarthritis (OA). Current antibody-based detection methods face limitations in identifying Mak targets. Here, we introduce an alkyne-functionalized probe, MA-diyne, which metabolically incorporates into proteins, enabling copper(I) ion-catalyzed click reactions to conjugate labeled proteins with azide-based fluorescent dyes or affinity purification tags. In-gel fluorescence confirms MA-diyne incorporation into proteins across various cell types and species, including mouse chondrocytes, adipocytes, Hek293T cells, and C. elegans . Pull-down experiments identified known Mak proteins such as GAPDH and Aldolase. The extent of MA-diyne modification was higher in Sirtuin 5-deficient cells suggesting these modified proteins are Sirtuin 5 substrates. Pulse-chase experiments confirmed the dynamic nature of protein malonylation. Quantitative proteomics identified 1136 proteins corresponding to 8903 peptides with 429 proteins showing 1-fold increase in labeled group. Sirtuin 5 regulated 374 of these proteins. Pull down of newly identified proteins such as β-actin and Stat3 was also done. This study highlights MA-diyne as a powerful chemical tool to investigate the molecular targets and functions of lysine malonylation in OA conditions.

Comparison of Early-Stage Knee Osteoarthritis Induced by Medial Meniscus Tear Versus Tibial Osteotomy in the Rat Model.

Medial meniscus tear (MMT) is a common method to induce osteoarthritis in rats, but mimics secondary osteoarthritis. A novel method of carrying out a medial wedge closing tibial osteotomy (TO) has been recently developed to induce primary osteoarthritis. This study aims to validate it, compared to MMT. Twenty rats were divided equally into 2 groups. Outcome measures such as histology graded according to Osteoarthritis Research Society International (OARSI) guidelines and computed tomography (CT) scans were analyzed at 6 weeks post-operatively. Observational gait analysis and serum biomarkers such as C-terminal cross-linked telopeptides of type II collagen (CTX-II) and interleukin-1 beta (IL-1β) were collected at 2-weekly intervals up to 6 weeks post-operatively. Serum CTX-II and IL-1β levels did not reveal a statistically significant difference across all time points between the 2 groups. CT grading was significantly more severe (2.80 ± 1.10 vs 1.40 ± 0.548, P = 0.0389) in the MMT group compared to the TO group. In addition, histological gradings such as calcified cartilage score (2.10 ± 1.91 vs 0.00 ± 0.00, P < 0.01) and cartilage degeneration score (4.80 ± 5.18 vs 0.00 ± 0.00, P < 0.01) revealed significantly more severe osteoarthritis in the MMT compared to TO group. Synovial membrane score did not reveal a statistically significant difference (1.10 ± 0.994 vs 1.00 ± 0.00, P = 1.00). TO is a novel method in inducing primary osteoarthritis in the rat model compared to MMT between the 6 and 12 weeks' time frame.

Knockdown of nuclear protein 1 delays pathological pro-gression of osteoarthritis through inhibiting chondrocyte ferroptosis

To investigate the effect of nuclear protein (Nupr) 1 on the pathological progression of osteoarthritis and its relationship with ferroptosis of chondrocytes. Chondrocytes from mouse knees were divided into small interfering RNA (siRNA) control group, small interfering RNA targeting Nupr1 (siNupr1) group, siRNA control+IL-1β group (siRNA control interference for 24 h followed by 10 ng/mL IL-1β) and siNupr1+IL-1β group (siNupr1 interference for 24 h followed by 10 ng/mL IL-1β). The protein and mRNA expressions of Nupr1 were detected by Western blotting and quantitative reverse transcription polymerase chain reaction (qRT-PCR). Cell proliferation viabilities were measured using the cell counting kit-8 method. The levels of ferrous ions were detected by FerroOrange staining. Lipid peroxidation levels were detected by C11-BODIPY-591 fluorescence imaging. The contents of malondialdehyde (MDA) and glutathione (GSH) were detected by enzyme-linked immunosorbent assay. The protein expressions of acyl-CoA synthetase long-chain family (ACSL) 4, P53, glutathione peroxidase (GPX) 4 and solute carrier family 7 member 11 gene (SLC7A11) were detected by Western blotting. The osteoarthritis model was constructed by destabilization of the medial meniscus (DMM) surgery in 7-week-old male C57BL/6J mice. The mice were randomly divided into four groups with 10 animals in each group: sham surgery (Sham)+adeno-associated virus serotype 5 (AAV5)-short hairpin RNA (shRNA) control group, Sham+AAV5-shRNA control targeting Nupr1 (shNupr1) group, DMM+AAV5-shRNA control group, and DMM+AAV5-shNupr1 group. Hematoxylin and eosin staining and Safranin O-Fast Green staining were used to observe the morphological changes in cartilage tissue. The Osteoarthritis Research Society International (OARSI) osteoarthritis cartilage histopathology assessment system was used to evaluate the degree of cartilage degeneration in mice. The mRNA expressions of matrix metallopeptidase (MMP) 13, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) 5, cyclooxy-genase (COX) 2, and GPX4 were detected by qRT-PCR. In vitro experiments showed that knocking down Nupr1 alleviated the decrease of chondrocyte proliferation activity induced by IL-1β, reduced iron accumulation in mouse chondrocytes, lowered lipid peroxidation, downregulated ACSL4 and P53 protein expression and upregulated GPX4 and SLC7A11 protein expression (all P<0.01), thereby inhibiting ferroptosis in mouse chondrocytes. Meanwhile, in vivo animal experiments demonstrated that knocking down Nupr1 delayed the degeneration of articular cartilage in osteoarthritis mice, improved the OARSI score, slowed down the degradation of the extracellular matrix in osteoarthritis cartilage, and reduced the expression of the key ferroptosis regulator GPX4 (all P<0.01). Knockdown of Nupr1 can delay the pathological progression of osteoarthritis through inhibiting ferroptosis in mouse chondrocytes.

Attenuating Cartilage Degeneration in a Low Mechanical Compression Rat Model Through Intra-Articular Injections of Allogeneic Bone Marrow-Derived Mesenchymal Stem Cells.

Mechanical stimulation significantly contributes to posttraumatic osteoarthritis (PTOA), a condition that impedes patient recovery following intra-articular injury. Effective treatment options for compression-induced injuries are limited. Bone marrow-derived mesenchymal stem cell (BMSC) implantation has emerged as a potential therapeutic breakthrough for joint diseases. The aim of this study was to attenuate the progression of PTOA induced by cyclic loading and demonstrate the potential effectiveness of BMSCs in a rat model of low mechanical compression. Using a rat model of compression-induced articular cartilage injury, assessments were conducted 2, 4, and 8 weeks after cyclic compressive loading. The expression of matrix metallopeptidase 13, transforming growth factor-beta 3 (TGF-β3), insulin-like growth factor 1 (IGF-1), and cleaved caspase-3 was evaluated through immunohistochemistry to investigate the mechanistic aspects underlying the prevention of compression-induced injury following BMSCs treatment. Intra-articular injections of BMSCs significantly improved scores in the OARSI (Osteoarthritis Research Society International) Osteoarthritis Cartilage Histopathology Assessment System and Histological-Histochemical Grading System. This treatment showed positive outcomes in maintaining high relative cell density and reducing proteoglycan loss after cyclic compression-induced injury. The expression patterns of IGF-1 and TGF-β3 provide valuable insights into the presence and distribution of these growth factors in healthy and injured cartilage. These findings highlight the efficacy of BMSCs treatment in attenuating the advancement of compression-induced injuries, albeit within a limited timeframe.

Soufeng sanjie formula alleviates osteoarthritis by inhibiting macrophage M1 polarization and modulating intestinal metabolites

Ethnopharmacological relevanceOsteoarthritis (OA) is defined as “bone bi” disease based on clinical symptoms in Chinese medicine. Soufeng sanjie formula (SF) is a traditional formula for treating “bone bi” disease, which consists of Scolopendra (dried body of Scolopendra subspinipes mutilans L. Koch) (0.5 g), Scorpions (dried body of Buthus martensii Karsch) (0.5 g), Astragali radix (dried root of Astragalus membranaceus (Fisch.) Bge) (20 g) and Black soybean seed coats (seed coats of Glycine max (L.) Merr) (30 g), and it can be used to treat rheumatoid arthritis. Nonetheless, the potential of SF to postpone the advancement of OA and its underlying mechanisms remain unexplored. Aim of the studyThis study investigated whether SF could alleviate OA and the underlying mechanisms. Materials and methodsAnterior cruciate ligament transection (ACLT) was performed to establish an OA mice model. Mechanical pain and cold pain were assessed to evaluate changes in pain sensitivity in OA mice. Micro-CT was used to observe the microstructure and quantify the bone morphological parameters of knee joints. Safranin O-fast green staining was used to evaluate cartilage damage, and Osteoarthritis Research Society International (OARSI) scores were calculated. Immunohistochemistry was used to assess the expression of inflammatory factors in the synovium of OA mice following SF administration. Immunofluorescence analyzed the fraction of CD80 and iNOS positive regions in the synovium of knee joints. The effect of SF on macrophage M1 polarization was investigated using flow cytometry, western blot and quantitative PCR (qPCR) in vitro. Untargeted metabolomics was used to identify the differential metabolites associated with OA. ResultsSF-treatment markedly reduced the cartilage damage, lowered the OARSI score and downregulated the pain sensitivity in the OA mice. Secondly, SF decreased the expression of IL-6, IL-1β, and TNF-α in the OA synovium. SF also reduced the percentage of CD80 and iNOS in the synovium of the knee joint after ACLT surgery by immunofluorescence. Thirdly, SF inhibited the protein expression of iNOS and COX-2, decreased the percentage of CD80, and reduced the mRNA levels of IL-6, IL-1β, and TNF-α in BMDM cells. Furthermore, SF inhibited the macrophage M1 polarization-related AKT/NF-κB signaling pathway. Finally, untargeted metabolomics showed that SF effectively reduced the levels of intestinal metabolite 18-hydroxyoleic acid in OA mice. ConclusionOur results suggested that SF reduced pain symptoms and joint inflammation in mice with OA. Furthermore, SF inhibited synovial macrophage M1 polarization and modified the levels of the pro-inflammatory intestinal metabolite 18-hydroxyoleic acid in OA mice. Therefore, SF may be act as a potential Chinese medicine for the treatment of OA.

Global trends and current research in post-traumatic osteoarthritis: A bibliometric and visualization analysis from 2010 to 2024.

To investigate global trends and current research on post-traumatic osteoarthritis (PTOA) from 2010 to 2024 using bibliometric and visualization techniques. A bibliometric analysis was conducted using data from the Web of Science Core Collection. The study examined publication trends, author contributions, institutional collaborations, keyword co-occurrence, and citation patterns, employing CiteSpace software to analyze key metrics such as publication frequency, centrality, and clustering. A total of 3100 articles were published between 2010 and 2024, with a steady increase over the years, peaking at 320 articles in 2023. Most publications were from the USA (1141 articles), China (502), and Germany (268), with key fields being Orthopedics, Surgery, and Rheumatology. Early research focused on different types of osteoarthritis, while recent studies highlight therapeutic advances such as cartilage repair and oxidative stress. Co-citation analysis identified influential authors like Lohmander LS, and key research clusters include total hip arthroplasty and regenerative medicine. Over the past decade, PTOA research has expanded substantially, driven by contributions from Orthopedics and Surgery, and supported by growing international collaboration, particularly between the United States, China, and European countries. Future research directions should prioritize elucidating the molecular mechanisms underlying PTOA, advancing diagnostic methodologies, and developing innovative therapeutic approaches to improve patient outcomes. The interdisciplinary nature and international cooperation observed are essential to addressing the complex challenges posed by PTOA.

Meniscus Injury Induces Patellofemoral Osteoarthritis Development Mediated by Synovitis and Gait Kinematics: A Preclinical Study.

To investigate whether meniscal injury leads to the development of patellofemoral (PF) osteoarthritis (PFOA) and to explore how synovitis and gait kinematics mediate this relationship. Fifty-four male Wistar rats (12 weeks old) were randomly assigned to the control, sham, or destabilized medial meniscus (DMM) groups. The rats were subjected to gait analysis to assess the kinematic changes at 2, 4, and 8 weeks postoperatively. Subsequently, the rats were euthanized, and their right knees were harvested for histological analysis. The Osteoarthritis Research Society International (OARSI) and modified Mankin (MM) scores in the DMM group were significantly higher than those in the control and sham groups at week 2 and significantly higher than those in the control group at week 4. The OARSI and MM scores in the sham group were significantly higher than those in the control group at weeks 2 and 4. The association between the DMM and OARSI scores was significantly mediated by the synovitis score and knee flexion angle at foot contact (proportion mediated: 58% and 10%, respectively). The association between the sham and OARSI scores was significantly mediated by the synovitis score and knee flexion angle (proportion mediated: 24% and 24%, respectively). DMM surgery induced articular cartilage damage in the PF joint. Synovitis and the knee flexion angle significantly mediated the association between DMM or sham surgery and PFOA development.