As the worldwide population ages, osteoarthritis has significantly increased. This musculoskeletal condition has become a pressing global health issue and thus, prevention and treatment of osteoarthritis have become the primary focus of domestic and international research. Scholarly investigations of the molecular mechanisms that are related to the occurrence and development of osteoarthritis have shed light on the pathological causes of this condition to a certain extent, providing a foundation for its prevention and treatment. However, further research is necessary to fully understand the critical role of the transcription factor SOX9 in chondrocyte differentiation and the development of osteoarthritis. As a result, there has been widespread interest in SOX transcription factors. While SOX9 has been utilized as a biomarker to indicate the occurrence and prognosis of osteoarthritis, investigations into other members of the SOX family and the development of targeted treatments around SOX9 are still required.

This article considers the impact of the SOX protein on the development and inhibition of osteoarthritis and highlights the need for therapeutic approaches targeting SOX9, as supported by existing research.

SOX9 can contribute to the process of osteoarthritis through acetylation and ubiquitination modifications. The regulation of the WNT signalling pathway, Nrf2/ARE signalling pathway, NF-κB signalling pathway and SOX9 is implicated in the emergence of osteoarthritis. Non-coding RNA may play a role in the onset and progression of osteoarthritis by modulating various SOX family members, including SOX2, SOX4, SOX5, SOX6, SOX8, SOX9 and SOX11.

SOX9 has the capability of mitigating the onset and progression of osteoarthritis through means such as medication therapy, stem cell therapy, recombinant adeno-associated virus (rAAV) vector therapy, physical therapy and other approaches.

Osteoarthritis (OA) is a cartilage-degenerative joint disease. Mitophagy impacts articular cartilage damage. tRNA-derived small RNAs (tsRNAs) are one of the contents of adipose mesenchymal stem cell (AMSC)-derived exosomes (AMSC-exos) and are involved in disease progression. However, whether tsRNAs regulate mitophagy and whether tsRNA-modified AMSC-exos improve OA via mitophagy remain unclear. We performed small RNA sequencing to identify OA-related tsRNAs, which were then loaded into AMSC-exos, exploring the function and mechanisms related to mitophagy in vitro and in vivo. Overall, 53 differentially expressed tsRNAs (DEtsRNAs) were identified between OA and normal cartilage tissues, among which 42 DEtsRNAs, including tsRNA-12391, were downregulated in the OA group. Target genes of tsRNA-12391 mainly participated in mitophagy-related pathways such as Rap1 signaling pathway. Compared to the control group, tsRNA-12391 mimics significantly promoted mitophagy, as shown by the upregulated expression of PINK1 and LC3 and the co-localization of Mito-Tracker Green and PINK1. Furthermore, tsRNA-12391 mimics effectively enhanced chondrogenesis in chondrocytes, as demonstrated by the elevated expression of collagen II and ACAN. AMSC-exos with tsRNA-12391 overexpression also facilitated mitophagy and chondrogenesis in vitro and in vivo. Mechanistically, tsRNA-12391 bound to ATAD3A restricted ATAD31 from degrading PINK1, leading to PINK1 accumulation. ATAD31 overexpression reversed the effects of tsRNA-12391 mimics on mitophagy and chondrogenesis. AMSC-exos loaded with tsRNA-12391 promoted mitophagy and chondrogenesis by interacting with ATAD31; this may be a novel therapeutic strategy for OA.

With the increasing prevalence of knee osteoarthritis (KOA), the limitations of traditional treatments, such as their limited efficacy in halting disease progression and their potential side effects, are becoming more evident. This situation has prompted scientists to seek more effective strategies. In recent years, exercise therapy has gained prominence in KOA treatment due to its safety, efficacy, and cost-effectiveness, which are underpinned by the molecular actions of exerkines. Unlike conventional therapies, exerkines offer specific advantages by targeting inflammatory responses, enhancing chondrocyte proliferation, and slowing cartilage degradation at the molecular level. This review explores the potential mechanisms involved in and application prospects of exerkines in KOA treatment and provides a comprehensive analysis of their role. Studies show that appropriate exercise not only promotes overall health, but also positively impacts KOA by stimulating exerkine production. The effectiveness of exerkines, however, is influenced by exercise modality, intensity, and duration of exercise, making the development of personalized exercise plans crucial for KOA patients. Based on these insights, this paper proposes targeted exercise strategies designed to maximize exerkine benefits, aiming to provide novel perspectives for KOA prevention and treatment.

Osteoarthritis (OA) is a degenerative joint disease that can be aggravated by synovitis and synovial immune disorders (SID). However, the role of synovial SID-related genes in OA synovium remains poorly understood. OA synovial and peripheral blood datasets were obtained from the GEO database ( https://www.ncbi.nlm.nih.gov/ ). Immune-related genes ( https://reactome.org/ ) showing differential expression in peripheral blood were identified as immune disorder genes. Subsequently, differentially expressed immune disorder genes in OA synovium were further identified as SID genes. The Venn diagram, random forest, SVM-RFE algorithm, and multivariate analysis were employed to determine SID-related hub genes in OA synovium. Using the identified hub genes, we constructed and validated a diagnostic model for predicting OA occurrence. The correlation between hub gene expression and immune-related modules was explored using CIBERSORT and MCP-counter analyses. We identified three SID-related hub genes (ACAT1, SPHK1, and ACACB) in OA synovium. The diagnostic model incorporating these hub genes demonstrated reliable predictive accuracy (AUC = 0.939). Through qPCR analysis, we quantitated the expression levels of the hub genes and confirmed that three hub genes could serve as novel biomarkers for OA patients (AUC = 0.960). Furthermore, we observed a significant correlation between the expression of these hub genes and immune cell infiltration, as well as inflammatory cytokine levels in OA synovium. Our findings suggest that three SID-related hub genes have the potential to serve as diagnostic biomarkers for OA patients. These genes are associated with immune disorder and contribute to immune alterations within the OA synovium.

Type 2 diabetes mellitus (T2DM) and Osteoarthritis (OA) share common risk factors like age, obesity and hypertension. Currently, 52 % of diabetic patients suffer from arthritis. Diabetes facilitates OA by altering lipid metabolism, levels of adipokines & cytokines, accumulation of advanced glycation end products, etc., which affects cartilage & bone health. However, the molecular mechanisms of the association of OA with T2DM remain unexplored. Since diabetes greatly affects the glycosylation status of proteins, the present study focused on identifying glycoproteins that could serve as diagnostic and prognostic markers for identifying osteoarthritis in diabetic individuals by LC-MS/MS. Comparative proteomic analysis revealed 20 significantly altered glycoproteins; among them, thyroxine-binding globulin (THBG), alpha-1-antitrypsin (A1AT), fibrinogen gamma chain (FGG) and angiotensinogen (AGT) were further validated. THBG, A1AT and AGT showed promising potential to identify the comorbid condition in serum and synovial fluid, however, ROC analysis identified THBG as the best candidate glycoprotein marker. Upregulation of THBG in OADM disrupts the bone remodeling cycle, degrades insulin, and promotes the expression of GLUT-1 and MMP-9. Overall, THBG could also serve as a therapeutic target for reducing the progression of osteoarthritis and alleviating pain and bone stiffness associated with the disease.

Osteoarthritis (OA) is characterized by pain, functional impairments, muscle weakness, and joint stiffness. Since OA heightens reliance on heath care resources and exacerbates socioeconomic burden, remote OA rehabilitation using digital technologies is rapidly evolving.

The aim of this study was to analyze the efficacy of behavioral therapy-based digital interventions for patients with OA.

This study is a systematic review of randomized controlled trials (RCTs) that assessed the effects of behavioral therapy-based digital intervention tools for OA. These RCTs were searched from inception to June 2023 in the Web of Science, Embase, Cochrane Library, Ovid, and PubMed databases.

Ten eligible RCTs comprising 1895 patients with OA were included. Digital tools based on either cognitive behavioral therapy (CBT) or behavior change technique (BCT) were investigated. All studies demonstrated low-to-moderate effects on pain reduction in the short term (standardized mean difference [SMD] -0.20, 95% CI -0.35 to -0.05). Six studies reported improvement in physical function (SMD -0.20, 95% CI -0.41 to 0.00), and 5 confirmed increased pain self-efficacy (SMD 0.22, 95% CI 0.02-0.42). In subgroup analysis, compared with CBT, BCT-based digital interventions demonstrated their effects on pain reduction (SMD -0.25, 95% CI -0.49 to 0.00) and physical function (SMD -0.26, 95% CI -0.54 to -0.01) in the short term. In addition, physiotherapist involvement in treatment had a positive effect on pain control (SMD -0.14, 95% CI -0.27 to -0.02). Furthermore, web-based digital tools improved physical function in the short term (SMD -0.28, 95% CI -0.54 to -0.01).

Moderate- and low-quality evidence supported that behavioral therapy-based digital tools improved pain intensity, physical function, and self-efficacy in the short term. However, affective interactions between patients and professionals may affect the clinical outcomes.

PROSPERO CRD42023430716; https://tinyurl.com/yc49vzyy.

Osteoarthritis (OA) is characterized by the degeneration of articular cartilage caused by several factors of which novel most trends include microbiota. Specific microbiota and the role in the development of OA is less clear. The microbiota is presumed to influence OA occurrence and progression mainly via immune modulation. In recent years, bone marrow mesenchymal stem cells (MSCs) have shown great potential for the treatment of OA, however, the therapeutic efficiency has been seriously affected by the harsh microenvironment in the joint cavity. At present, many strategies have been used to enhance the function of MSCs, among them, engineering are a promising method. Therefore, this review mainly focuses on the latest research on how the microbiota affects the development of OA, stem cell repair, and the use of engineered MSCs in the treatment of OA. In addition, engineered MSCs can enhance the therapeutic potential of exosomes as a novel strategy for treating OA. Our review provides a comprehensive perspective on the role of microbiota in OA and the influence of MSCs therapy and engineered MSCs on the treatment of OA.

Our study aimed to provide global burden and temporal trends in the incidence, prevalence, and disability-adjusted life-years (DALYs) of osteoarthritis (OA) among postmenopausal women from 1990 to 2021.

The study employed data from the Global Burden of Disease (GBD) Study 2021. Four subtypes of OA affecting the hip, knee, hand, and other joints among postmenopausal women were included. Age-standardised rates (ASRs) were derived with reference to the global age standard, and temporal patterns were scrutinised through estimated annual percentage change (EAPC) assessments. The impact of age, body mass index (BMI), and Socio-demographic Index (SDI) were all considered.

From 1990 to 2021, there were more than 1.3-fold increases in OA incidence, prevalence, and DALYs among postmenopausal women globally, with EAPCs of 0.211, 0.356, and 0.395, respectively. Knee OA carried the heaviest burden, while hip OA bore the least. Higher SDI regions had higher burden, and inequalities linked to SDI among countries had intensified over time. East Asia and high-income Asia Pacific experienced the most substantial increments in OA burden. High BMI significantly influences the burden of OA, especially in countries within high, high-middle, and middle SDI, where DALYs attributed to high BMI exceed 20%.

The burden of OA among postmenopausal women continues to escalate, highlighting its significant impact on the global health of postmenopausal women. Necessarily, effective monitoring and management of risk factors, targeted lifestyle adjustments for BMI, and policy interventions accounting for demographic disparities are required to ease OA in postmenopausal women.

Osteoarthritis (OA) is a prevalent articular disorder characterized by joint degeneration and persistent pain; it imposes a significant burden on both individuals and society. While OA has traditionally been viewed as a localized peripheral disorder, recent preclinical and clinical studies have revealed the crucial interconnections between the bone and the brain, highlighting the systemic nature of OA. The neuronal pathway, molecular signaling, circadian rhythms, and genetic underpinnings within the bone-brain axis play vital roles in the complex interplay that contributes to OA initiation and progression. This review explores emerging evidence of the crosstalk between the bone and brain in OA progression, and discusses the potential contributions of the bone-brain axis to the development of effective interventions for managing OA.

This study aims to define Kellgren-Lawrence grade (KLG) using OARSI grade and stratify radiographic knee osteoarthritis (KOA) into distinct phenotypes based on radiographic structure changes and compare clinical symptoms and disease progression.

We used radiographic grading data provided by the OAI and MOST study. Decision tree was used to (1) Find OARSI grade criteria for each KLG and (2) Phenotype early osteoarthritic knees (=KLG1, 2) by the radiographic structure changes. Pain, function, and progression to KLG ≥3 were compared between phenotypes.

10,804 knees from 5802 patients were included. The mean follow-up duration was 55.6 ​± ​24.5 months. Criteria for KLG1 was: (1) Joint space narrowing (JSN) grade (more severe grade among medial and lateral compartments) ​= ​1 without osteophytes (i.e., KLG1Jt) (2) A single grade 1 osteophyte without JSN (i.e., KLG1Ost). Criteria for KLG2 was (1) JSN ​= ​1 with a sum of osteophyte grades ≥1 (i.e., KLG2Jt): (2) Sum of osteophyte grades ≥2 without JSN (i.e., KLG2Ost). In terms of pain and function, there was no difference between KLG1Ost and KLG1Jt or between KLG2Ost and KLG2Jt. For progression to KLG ≥3, the mean survival time of KLG1Ost was 1.87-fold (95 ​% CI: 1.31-2.67) longer than that of KLG1Jt, while KLG2Ost was 5.42-fold (95 ​% CI: 3.69-7.96) longer than KLG2Jt.

We proposed the criteria for each KLG using OARSI grade and phenotypes characterized by radiographic structure deformity in early KLG. Within the same KLG, the rate of disease progression was different depending on the structural deformity.

This overview aims to assess the methodological and evidence quality of systematic reviews related to radiofrequency ablation (RFA) for knee osteoarthritis (KOA).

A comprehensive search strategy was conducted through two independent researchers in eight electronic databases from the inception to September 1, 2024. The methodological quality of the included systematic reviews was assessed by the Assessing the Methodological Quality of Systematic Reviews 2 tool. The Grading of Recommendations Assessment, Development, and Evaluation tool assessed the evidence quality.

Eight systematic reviews were finally included. The results of the methodological quality of the included systematic reviews were generally unsatisfactory. The limitations were a lack of pre-designed protocols, reasons for the inclusion of study types, a list of excluded studies, the consideration of the single study risk of bias, and management of conflicts of interest. A total of 56 outcome indicators were evaluated, with one item receiving a moderate quality rating, while the rest were classified as low or very low. Limitations were identified as the primary factors leading to the downgrade.

RFA shows efficacy in treating KOA, with tolerable side effects. However, systematic reviews' poor quality indicates cautious interpretation needed. Future studies must enhance quality for robust EBM.

Recent research indicated a strong link between the gut microbiota and osteoarthritis. However, the complex interplay between the gut microbiota, serum metabolites, and the progression of osteoarthritis in affected individuals remains largely unexplored. This study aimed to investigate the characteristics of the gut microbiota and serum metabolites in patients with osteoarthritis.

Participants with either healthy knees or osteoarthritis were enrolled and categorized into healthy control (HC) and osteoarthritis (OA) groups. Fecal and blood samples were collected for 16S rRNA gene sequencing, metabolomic analysis via liquid chromatography-mass spectrometry (LC-MS), and integrated evaluation.

The results showed no significant variation in gut microbiota richness and diversity between the two groups. However, the abundance of Bacteroides plebeius and Faecalibacterium prausnitzii was reduced in the OA group, both of which are known for their potential as next-generation probiotics for human health. Metabolomic analysis indicated that serum metabolites, including pyrogallol and 3-hydroxybutyrate (3HB), were significantly lower in the OA group. These metabolites are known to positively impact osteoarthritis progression and other diseases and demonstrated good diagnostic performance for distinguishing osteoarthritis patients from healthy controls. Correlation analysis revealed a positive correlation between Bacteroides plebeius and Faecalibacterium prausnitzii and between pyrogallol and 3HB.

This study highlighted specific gut microbiota and serum metabolite profiles in osteoarthritis patients, suggesting that the specific changes in bacteria and derived metabolites are closely tied to osteoarthritis progression. This underscores the potential of gut microbiota and serum metabolites as modifiable elements and therapeutic targets for osteoarthritis prevention.

Osteoarthritis (OA) is a chronic multifactorial disease characterized by cartilage degeneration, pain, and reduced mobility. Current therapies primarily aim to relieve pain and restore function, but they often have limited effectiveness and side effects. Coixol, a bioactive compound from Coix lacryma-jobi L., exhibits anti-inflammatory and analgesic properties, suggesting potential benefits in OA treatment. This study explored the effects of coixol on OA chondrocytes. Primary chondrocytes from OA rats were isolated and treated with varying concentrations of coixol. Cell viability and proliferation were assessed by using CCK-8 assays. The expression of genes related to ferroptosis and autophagy was analyzed through RT-qPCR, Western blot, and immunofluorescence. Moreover, the study investigated the characteristics and performance of coixol-loaded PDLLA-PEG-PDLLA (PLEL)/gelatin sponge (GS) hydrogels (Coixol@PLEL/GS) for enhancing osteochondral defect repair by specifically targeting chondrocyte ferroptosis and autophagy. The characteristics of coixol-loaded PDLLA-PEG-PDLLA/gelatin sponge (Coixol@PLEL/GS) hydrogels were evaluated using cryo-scanning electron microscopy (SEM) or SEM, and coixol release kinetics were determined. In vivo, a rat osteochondral defect model was used to assess the efficacy of Coixol@PLEL/GS in osteochondral defect repair using International Cartilage Repair Society (ICRS) scores, Safranin O/Fast green staining, Toluidine blue staining, and immunofluorescence. Coixol significantly increased the viability and proliferation of OA chondrocytes in a dose-dependent manner. Furthermore, coixol inhibited ferroptosis and stimulated autophagy, as evidenced by the upregulation of related genes. In vivo, Coixol@PLEL/GS remarkably enhanced the repair of osteochondral defects compared to that of control groups. In conclusion, coixol protects OA chondrocytes by improving survival, inhibiting ferroptosis, and activating autophagy, highlighting its potential as a therapeutic strategy for OA treatment.

This study aims to explore the relationship between osteoarthritis and the trace elements zinc and copper and to provide a theoretical basis for research on the related mechanisms for the prevention, diagnosis, and treatment of osteoarthritis. We searched all the literature indexed in Web Of Science, Embase, and PubMed as of January 10, 2024, summarized the zinc and copper detection indexes in patients with osteoarthritis, obtained clinical data through literature screening, quality assessment, and data extraction, and analyzed the data using Revman 5.4. A total of 13 papers were included in this study, totaling 7983 study subjects. These were divided into osteoarthritis and healthy control groups. The results from the meta-analysis showed that in patients with osteoarthritis, circulating copper levels, but not zinc levels, were significantly higher compared to healthy individuals. The level of copper in the blood of patients with osteoarthritis is significantly higher than that of healthy people.

Traditional Chinese medicine (TCM) is frequently used to treat osteoarthritis (OA). Duhuo Jisheng decoction (DHJSD), a Chinese patent medicine, was commonly used Chinese herbal formula for the treatment of OA. In Western medicine, dual inhibition of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) enzyme has been proved to be a promising strategy to treat inflammatory diseases with reduced side effects.

To elucidate the dual action mechanism of DHJSD targeting COX-2 and 5-LOX against OA.

DHJSD, containing 1495 compounds was screened using a virtual screening approach based on molecular docking. The inhibitory effect of hit compounds against COX-2 and 5-LOX was validated using enzyme-based assays. In vitro, rat chondrocytes were treated with IL-1β (10 ng/mL) for 24 h to induce OA model in vitro. The chondrocyte viability was evaluated using an CCK-8 assay. ELISA was used to detect inflammatory factors expression. Immunofluorescence was used to assess the expression level of collagen II and MMP-13. In addition, a rat cartilage explants culture model was established, and safranin O and HE staining analysis were carried to assess cartilage matrix degradation and cartilage damage, respectively. In vivo, carrageenan-induced paw edema assay was used to examine anti-inflammatory activity, and the gastric ulcerogenic effect was further detected. Finally, Molecular dynamics simulations and binding free energy analysis were carried to explore the binding mechanism.

13 compounds from DHJSD were identified as promising candidates by a virtual screening approach. Among these candidates, three hits 7,4'-dimethoxyisoflavone, genistein, and fraxetin displayed dual inhibition of COX-2 and 5-LOX. Further in vitro assay indicated that 7,4'-dimethoxyisoflavone, genistein, and fraxetin could inhibit PGE2, LTB4, TNF-α, IL-6, or NO production in IL-1β-induced chondrocytes. In addition, the three compounds reduced IL-1β-induced degradation of collagen II and expression of MMP-13 in rat chondrocytes. The results of anti-inflammatory activity of the three compounds in vivo showed that the highest anti-inflammatory activity with edema inhibition percentages of 50.00%, 56.00%, and 51.00% after 3 h, respectively. Moreover, it was found that 7,4'-dimethoxyisoflavone, genistein, and fraxetin have a superior gastric safety profile comparable to indomethacin. Finally, molecular dynamics simulations, binding free energy analysis, and detailed interaction mode demonstrated that 7,4'-dimethoxyisoflavone, genistein, and fraxetin interacted well with both COX-2 and 5-LOX.

7,4'-dimethoxyisoflavone, genistein, and fraxetin from DHJSD with excellent anti-inflammatory effects and no gastric ulceration effects, which helps to explain the dual action mechanism and potential material basis of DHJSD in treating OA and provide evidence to support DHJSD's clinical use.

tRNA-derived fragments (tRFs) are novel short noncoding RNAs that play pivotal roles in cell proliferation and survival. However, knowledge of the biological roles of tRFs in anterior cruciate ligament (ACL) cells is limited. Here, we intended to investigate the function of tRF-3031B in ACL cell. We used the tRF and tiRNA array to analyze tRF and tiRNA expression profiles in osteoarthritis (OA) ACL cells and normal ACL cells, and qRT-PCR and fluorescence in situ hybridization (FISH) were used to determine tRF-3031B expression. The results showed that tRF-3031B was expressed at low levels in OA ACL and Interleukin-1β (IL-1β) treated ACL cells. We found that RELA was the target of tRF-3031B. When ACL cells were transfected with tRF-3031B mimics, RELA expression was suppressed, whereas transfection with tRF-3031B inhibitors had the opposite effect. The rescue and dual-luciferase reporter assays showed that tRF-3031B silenced the RELA expression by binding to its untranslated region (3'-UTR). Hence, this study showed the novel function of tRF-3031B in regulating ACL cell proliferation and survival by targeting RELA, and these findings may offer a new direction for the study of ACL degeneration and pathophysiological of OA.

Osteoarthritis (OA) is a chronic degenerative joint disorder characterized by an imbalance in chondrocyte metabolism. Ferroptosis has been implicated in the pathogenesis of OA. The role of Sirt1, a deacetylase, in mediating deacetylation during ferroptosis in OA chondrocytes remains underexplored. This study aimed to elucidate the mechanisms by which Sirt1 influences chondrocyte ferroptosis in the development of OA.

In vitro and in vivo models of OA were established using IL-1β-induced mouse chondrocytes and a destabilization of the medial meniscus (DMM) mouse model, respectively. Ferroptosis was evaluated through measurements of cell viability, lactate dehydrogenase (LDH) release, intracellular levels of Fe2+, glutathione (GSH), malondialdehyde (MDA), lipid reactive oxygen species (ROS), propidium iodide staining, and Western blot analysis. The underlying mechanisms were further investigated using quantitative real-time polymerase chain reaction, Western blotting, immunoprecipitation (IP), co-immunoprecipitation (Co-IP), and glutathione-S-transferase pulldown assays. In vivo validation was performed via Safranin O staining.

IL-1β induced ferroptosis and increased histone acetylation, effects that were partially reversed by Sirt1 overexpression. Mechanistically, Sirt1 overexpression upregulated ferritin light polypeptide (Ftl) expression by deacetylating Ftl at the K181 residue. Ftl knockdown inhibited the ferroptosis-enhancing effect of Sirt1 overexpression in chondrocytes. In vivo studies showed that Sirt1 overexpression mitigated the progression of OA and reduced ferroptosis in the DMM-induced OA mouse model.

Our findings confirm that Sirt1 overexpression promotes Ftl expression through deacetylation at the K181 site, thereby suppressing chondrocyte ferroptosis and attenuating the progression of OA. These results suggest a potential therapeutic target for OA treatment.

Osteoarthritis (OA) is a degenerative musculoskeletal disease, featured by the destruction of articular cartilage. Oxidative stress, one of the drivers of the extracellular matrix degradation in cartilage, plays a vital role in OA pathogenesis. Senkyunolide I (SEI) is a natural compound with a prominent anti-oxidative stress property against multiple diseases. However, the protective effect of SEI on OA has not been explored. Here, we aimed to elucidate the effect of SEI on OA in vitro. Our results showed that SEI suppressed the expression of senescence-related markers such as P16 and P21 in IL-1β-induced chondrocytes. Besides, SEI alleviated IL-1β-induced the degradation of extracellular matrix (ECM) by suppressing the matrix proteinase like MMP13 and ATAMDS5 while promoting matrix synthesis regulated biomarkers like COL2A1 and ACAN in chondrocytes. Mechanically, the mitochondrial dysfunction and overproduction of intracellular reactive oxygen species (ROS) in chondrocytes induced by IL-1β were reversed by SEI. Additionally, the ROS inhibitor N-acetylcysteine (NAC) synergistically enhanced the biological effect of SEI in IL-1β-induced chondrocytes. Moreover, it was also found that the expression of Nrf2 and HO-1 was increased by the treatment of SEI in IL-1β-stimulated chondrocytes, while the Nrf2 inhibitor ML385 reversed the protective effect of SEI on OA chondrocytes. In conclusion, SEI could inhibit senescence, the degradation of ECM, and the production of ROS through activating Nrf2/ HO-1 signaling pathway, which provide a novel candidate for OA treatment.

Peri-prosthesis osteolysis (PPO) represents the most severe complication of total joint arthroplasty (TJA) surgery and imposes the primary cause of prosthesis failure and subsequent revision surgery. Antiresorptive therapies are usually prescribed to treat PPO, especially for elderly people. Nevertheless, the efficacy of anti-osteoporotic medications remains constrained. Recent therapeutic strategies to promote periprosthetic osseointegration by restoring osteoblast function are considered more effective approaches. However, the precise mechanism underlying the inhibition of osteogenesis triggered by wear particles remains enigmatic. Herein, we demonstrate that wear particles inhibit osteoblast function by inducing ferroptosis to sabotage extracellular mineralization and arouse periprosthetic osteolysis. The suppression of ferroptosis could significantly rescue osteogenesis thus alleviating PPO. Furthermore, Glutathione Peroxidase 4 (GPX4) has been identified as a key target in regulating osteoblastic ferroptosis. By utilizing virtual screening techniques, we have successfully conducted a comprehensive screening of a natural compound known as Urolithin A (UA), which exhibits remarkable inhibition of osteoblastic ferroptosis while simultaneously promoting the process of osteogenesis through its precise targeting mechanism on GPX4. Meanwhile, UA improves the osteolytic conditions significantly in vivo even when the adjunction of titanium (Ti) nanoparticles. This strategy has great potential in treating peri-prosthesis osteolysis and potentially broadens the scope of clinical therapy.

This meta-analysis and systematic review aimed to comprehensively investigate the effects of vitamin K supplementation on bone mineral density (BMD) at various sites and bone metabolism in middle-aged and older adults.

The databases of PubMed, Web of Science, and Cochrane Library were thoroughly searched from inception to July 2023.

The results revealed that vitamin K supplementation increased BMD at the lumbar spine (p = 0.035). Moreover, the pooled effects demonstrated a notable increase in carboxylated osteocalcin (cOC) (p = 0.004), a decrease in uncarboxylated osteocalcin (ucOC) (p < 0.001), and no significant effect on total osteocalcin (tOC) (p = 0.076). Accordingly, the ratio of cOC to ucOC (p = 0.002) significantly increased, while the ratio of ucOC to tOC decreased (p = 0.043). However, there was no significant effect of vitamin K supplementation on other bone metabolism markers, such as cross-linked telopeptide of type 1 collagen (NTx), bone alkaline phosphatase (BAP), and procollagen I N-terminal propeptide (PINP). Subgroup analysis revealed that vitamin K notably enhanced bone health in females by increasing lumbar spine BMD (p = 0.028) and decreasing ucOC (p < 0.001). Vitamin K, especially vitamin K2, exhibited effects on maintaining or increasing lumbar spine BMD, and influencing the balance of cOC and ucOC.

This review suggests that the beneficial effects of vitamin K supplementation on bone health primarily involve enhancing the carboxylation of OC rather than altering the total amount of OC.

To explore the barriers and enablers to providing and receiving primary care for osteoarthritis (OA) in Ireland from the perspectives of primary care healthcare professionals (HCPs) and individuals with OA.

Descriptive qualitative study incorporating an inductive thematic analysis to identify key barrier and enabler themes and subsequent deductive mapping to the Theoretical Domains Framework (TDF).

Primary care in Ireland.

HCPs, including 6 general practitioners, 5 physiotherapists, 1 occupational therapist and 1 practice nurse, and 13 individuals with OA were interviewed.

Identified barriers and enablers related to nine domains of the TDF. Key barriers identified by HCPs included limited and delayed access to multidisciplinary primary care services, lack of integrated care pathways specific to OA and insufficient training in musculoskeletal conditions including OA. Individuals with OA also reported poor access to health services due to long waiting lists, lack of education on OA and feelings of not being taken seriously by HCPs. There is a need for targeted HCP education and training to address the identified knowledge, skills and confidence gaps in communication, diagnosis and evidence-based management of OA. Improved management of OA through system-level changes, including integrated care pathways with multidisciplinary services to better support individuals with OA in the community, is required.

This study identified several barriers and enablers to the management of OA. These findings highlight areas to be targeted by future interventions aimed at improving the management of OA in primary care.

Osteoarthritis (OA) is a prevalent degenerative joint condition, and emerging evidence suggests that dietary factors, such as coffee consumption, may influence its risk. However, the relationship between coffee consumption and the risk of developing OA remains ambiguous. This study aims to explore the association between coffee intake and OA complemented by Mendelian randomization (MR) to infer causality.

We analyzed data from 32,439 participants across 10 NHANES cycles (1999-2018), including 3,676 individuals diagnosed with OA. Osteoarthritis was diagnosed through a structured questionnaire, while coffee consumption was assessed via 24-h dietary recalls. Participants were categorized based on reported coffee intake: 0 cups, <2 cups, 2-4 cups, and >4 cups per day. We employed weighted multivariable logistic regression to examine associations between coffee consumption and OA by using data from the NHANES 1999-2018, adjusting for various covariates. Subsequently, a MR analysis was conducted using genetic variants as instrumental variables to infer causal relationships, with multiple methods including inverse-variance weighted (IVW) analysis, MR-Egger regression, and weighted median techniques to assess the robustness, heterogeneity, and potential pleiotropy of our findings.

Our regression models indicated an increased risk of OA with rising coffee consumption, with significant associations noted particularly for those consuming more than 4 cups daily (OR = 1.19, 95% CI: 1.00-1.41, p = 0.049). In MR analysis, coffee intake was causally linked to OA types, demonstrating increased risk for knee OA (KOA: OR = 1.60, 95% CI: 1.08-2.35, p = 0.018), hip OA (HOA: OR = 1.85, 95% CI: 1.06-3.25, p = 0.031), and combined KOA and HOA (KHOA: OR = 1.66, 95% CI: 1.18-2.33, p = 0.003). Sensitivity analyses confirmed the stability of results across multiple evaluation methods.

Our findings highlight a significant association between coffee consumption and an increased risk of OA, suggesting that higher intake levels may contribute to OA morbidity. These results warrant further exploration into the underlying biological mechanisms and implications for dietary guidelines in populations at risk for OA.

Joint degeneration characterized by cartilage deterioration and bone wear is the hallmark of osteoarthritis (OA), a condition that worsens over time. Total knee arthroplasty (TKA) is the most common effective treatment for OA. Conventional therapy training (CTT) is the standard intervention; we are testing whether intensive therapy training (ITT) provides different results when used preoperatively. Our study compared intensive and standard preoperative physical therapy in randomized and non-randomized controlled trials, excluding various other study types. Two independent researchers assessed the risk of bias using appropriate tools (RoB 2 for RCTs (Cochrane Methods, London, UK) and ROBINS-I for non-randomized studies (Cochrane Methods, London, UK)). The analysis, conducted using ReviewManager 5.4 (Cochrane Methods, London, UK), presented results as mean differences (MD) with 95% CIs, employing fixed or random-effects models based on heterogeneity assessments. With a total number of 490 participants, ITT showed significant improvements in the six or 10-minute walk test (MD = 45.07m, P < 0.000001), quadriceps strength (MD = 0.07 Kg, P < 0.0001), range of motion (ROM) flexion (MD = 4.29, P = 0.03), isometric knee flexion (MD =2.32, P=0.04), SF-36 physical component (MD = 1.19, P <,0.0001), stair test (MD = -2.01, P = 0.01), timed up and go test (MD = -1.12, P = 0.02), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score (MD = -8.43, P = 0.002). Conversely, CTT showed better results in isometric knee extension (MD = 3.45, P = 0.02). No significant differences were found in ROM extension or visual analog score (VAS) pain scores. Preoperative ITT demonstrates overall superior outcomes compared to CTT for total knee arthroplasty patients. ITT significantly improved various functional and patient-reported outcomes, including walking capacity, quadriceps strength, range of motion, and quality of life measures. However, CTT showed superiority in isometric knee extension. We recommend implementing preoperative ITT protocols for TKA patients while acknowledging the need for further research to optimize exercise specifics, frequency, and duration for optimal results.

Arthritis and low back pain (LBP) are prevalent musculoskeletal conditions with a perceived association. Previous observational studies have suggested a possible link between arthritis and LBP, but causality has not been firmly established.

The analysis involved data from a meta-analysis of genome-wide association studies sourced from the UK Biobank Genetics resources on rheumatoid arthritis (RA), osteoarthritis (OA) at any site, knee osteoarthritis (KOA), hip osteoarthritis (HOA), and LBP. Two-sample Mendelian randomization analysis was utilized to evaluate the causal link between arthritis and LBP. The primary method employed was inverse-variance weighting (IVW), with additional techniques such as MR-Egger, weighted median, Cochran Q statistic, and leave-one-out analysis used to identify heterogeneity and pleiotropy.

Genetically determined RA exhibited a causal impact on LBP (Weighted median: odds ratio [OR] = 1.094, 95% confidence interval [CI] 1.002-1.195, p = 0.043). Furthermore, OA at any site and KOA showed causal associations with LBP (Inverse variance weighted: OR = 1.089, 95% CI 1.011-1.173, p = 0.026) and (OR = 1.0004, 95% CI 1.000-1.008, p = 0.019), respectively. Additionally, HOA was also linked causally with an elevated risk of developing LBP (Weighted median: OR = 1.002, 95% CI 1.000-1.004, p = 0.049; Inverse variance weighted: OR = 1.002, 95% CI 1.001-1.004, p = 0.003).

This study offers genetic evidence supporting the causal relationship between RA, OA at any site, KOA, HOA and the increased risk of LBP, especially highlighting the significant impact of HOA.

Chondrocyte senescence and inflammation are hallmarks of osteoarthritis (OA). Forsythiaside A (FTA), a phenylethanol glycoside isolated from air-dried fruits of Forsythia, has been reported to have significant anti-inflammatory and antioxidant properties. However, its protective effects against OA have not been elucidated.

We explored the therapeutic efficacy of FTA in inhibiting chondrocyte senescence and inflammation during OA, as well as the potential underlying mechanisms.

This study aimed to investigate the novel mechanism of FTA in alleviating OA in both cell and animal models.

The protective effect of FTA against tert‑butyl hydroperoxide-induced chondrocyte damage was assessed, and the effects of FTA on cartilage aging and OA progression were evaluated using a medial meniscus (DMM)-induced knee OA mouse model. The regulatory effects of FTA on the NLRP3 Inflammasome, mitophagy, and the PKC/Nrf2 pathway were also explored.

In vitro, FTA improved mitochondrial function, enhanced mitophagy, suppressed NLRP3 inflammasome activation, and inhibited chondrocyte senescence; however, these chondroprotective effects were partially reversed after mitophagy inhibition, NLRP3 inflammasome activation, and Nrf2 pathway inhibition. Furthermore, we found that FTA directly interacts with Nrf2 and enhances its phosphorylation by protein kinase C (PKC). In vivo, FTA attenuated the pathological signs of knee OA in a DMM-model mouse model, which was partially reversed by ML385.

FTA inhibited chondrocyte senescence and OA progression by activating the PKC-Nrf2 pathway. Thus, FTA is a potential novel therapeutic agent for OA.

Clusterzymes are synthetic enzymes exhibiting substantial catalytic activity and selectivity, which are uniquely driven by single-atom constructs. A dramatic increase in antioxidant capacity, 158 times more than natural trolox, is noted when single-atom copper is incorporated into gold-based clusterzymes to form Au24Cu1. Considering the inflammatory and mildly acidic microenvironment characteristic of osteoarthritis (OA), pH-dependent dendritic mesoporous silica nanoparticles (DMSNs) coupled with PEG have been employed as a delivery system for the spatial-temporal release of clusterzymes within active articular regions, thereby enhancing the duration of effectiveness. Nonetheless, achieving high therapeutic efficacy remains a significant challenge. Herein, we describe the construction of a Clusterzymes-DMSNs-PEG complex (CDP) which remarkably diminishes reactive oxygen species (ROS) and stabilizes the chondroprotective protein YAP by inhibiting the Hippo pathway. In the rabbit ACLT (anterior cruciate ligament transection) model, the CDP complex demonstrated inhibition of matrix metalloproteinase activity, preservation of type II collagen and aggregation protein secretion, thus prolonging the clusterzymes' protective influence on joint cartilage structure. Our research underscores the efficacy of the CDP complex in ROS-scavenging, enabled by the release of clusterzymes in response to an inflammatory and slightly acidic environment, leading to the obstruction of the Hippo pathway and downstream NF-κB signaling pathway. This study illuminates the design, composition, and use of DMSNs and clusterzymes in biomedicine, thus charting a promising course for the development of novel therapeutic strategies in alleviating OA.

The RNA-binding protein DDX3X is associated with several biological processes including inflammation and immunity. However, the role of DDX3X in the pathology of inflammation-related osteoarthritis (OA) remains unclear. This study was to explore the action of DDX3X in the progression of OA as well as the underlying mechanisms by using RNA immunoprecipitation (RIP), Immunohistochemical (IHC) and DDX3X knockout mice, etc. We found that DDX3X expression was upregulated in cartilage tissue of OA patient. The in vitro study also showed upregulation of DDX3X in the inflammatory chondrocytes stimulated by LPS. DDX3X overexpression reduced cell viability by inducing pyroptosis in chondrocytes. Knockdown of DDX3X rescued LPS-induced chondrocytes pyroptosis through regulating NLRP3 signaling. In addition, DDX3X deletion attenuates osteoarthritis in vivo. In conclusion, DDX3X promotes OA progression by regulating chondrocytes pyroptosis via the activation of NLRP3 signaling.

Background/Objectives: The interest in performing total ankle arthroplasty (TAA) to address end-stage ankle osteoarthritis (OA) is continuously growing. Sports activity plays an important role in our world. The literature is sparse regarding return-to-sports activity following TAA. The levels and types of sports in TAA are rarely reported. The purpose of this prospective case series study is to investigate sports activity in ankle osteoarthritis (OA) and TAA in terms of rate, frequency, type, and clinical outcomes with a minimum 2 years of follow-up after surgery. Methods: A total of 103 patients (105 implants, 52 female, and 51 male), mean age 60.5 years (range, 23-84 years) with end-stage ankle OA were treated using a three-component, uncemented, mobile-bearing VANTAGE Total Ankle System. The mean follow-up was 2.9 years (range, 2-5 years). Visual Analogic Scale Pain Score (VAS, 0-10 points), Ankle Dorsiflexion/Plantarflexion (DF/PF) range of motion (ROM; degrees), functional American Orthopaedic Foot and Ankle Society (AOFAS) Ankle/Hindfoot Score (0-100 points), Subjective Patients' Satisfaction Score (0-10 points), Sports Activity Rate, Sports Frequency Score, and sports type were assessed. Results: The mean preoperative VAS Pain Score was 6.7 points (range, 3-10 points) and 0.2 points for postoperative (range, 0-3 points) (p < 0.001). The mean DF/PF ROM was 24.9° preoperative (range, 0-60°) and 52.9° postoperative (range, 15-85°) (p < 0.001). The mean preoperative functional AOFAS Ankle/Hindfoot Score was 39.5 points (range, 4-57 points) and 97.8 points for postoperative (range, 75-100 points) (p < 0.001). The mean postoperative Subjective Patients' Satisfaction Score was 9.7 points (range, 7-10 points). The preoperative Sports Activity Rate was 31.1%, with 85.4% for postoperative (p < 0.001). All the groups exhibited substantial Sports Frequency Score increases (p < 0.001). The most practised sports were hiking, biking, fitness, and swimming. Conclusions: total ankle arthroplasty (TAA) is an effective treatment for end-stage ankle OA. TAA facilitates a noteworthy increase in sports activity. This research offers important sports insights to patients with ankle OA and TAA.

Osteoarthritis (OA) is a common degenerative disease. PA28γ is a member of the 11S proteasome activator and is involved in the regulation of several important cellular processes, including cell proliferation, apoptosis, and inflammation. This study aimed to explore the role of PA28γ in the occurrence and development of OA and its potential mechanism.

A total of 120 newborn male mice were employed for the isolation and culture of primary chondrocytes. OA-related indicators such as anabolism, catabolism, inflammation, and apoptosis were detected. Effects and related mechanisms of PA28γ in chondrocyte endoplasmic reticulum (ER) stress were studied using western blotting, real-time polymerase chain reaction (PCR), and immunofluorescence. The OA mouse model was established by destabilized medial meniscus (DMM) surgery, and adenovirus was injected into the knee cavity of 15 12-week-old male mice to reduce the expression of PA28γ. The degree of cartilage destruction was evaluated by haematoxylin and eosin (HE) staining, safranin O/fast green staining, toluidine blue staining, and immunohistochemistry.

We found that PA28γ knockdown in chondrocytes can effectively improve anabolism and catabolism and inhibit inflammation, apoptosis, and ER stress. Moreover, PA28γ knockdown affected the phosphorylation of IRE1α and the expression of TRAF2, thereby affecting the mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signalling pathways, and finally affecting the inflammatory response of chondrocytes. In addition, we found that PA28γ knockdown can promote the phosphorylation of signal transducer and activator of transcription 3 (STAT3), thereby inhibiting ER stress in chondrocytes. The use of Stattic (an inhibitor of STAT3 phosphorylation) enhanced ER stress. In vivo, we found that PA28γ knockdown effectively reduced cartilage destruction in a mouse model of OA induced by the DMM surgery.

PA28γ knockdown in chondrocytes can inhibit anabolic and catabolic dysregulation, inflammatory response, and apoptosis in OA. Moreover, PA28γ knockdown in chondrocytes can inhibit ER stress by promoting STAT3 phosphorylation.

Osteoarthritis (OA) is the most prevalent degenerative joint disease, marked by cartilage degeneration, synovitis, and subchondral bone changes. The absence of effective drugs and treatments to decelerate OA's progression highlights a significant gap in clinical practice. Ferroptosis, an iron-dependent cell death driven by lipid peroxidation, has emerged as a research focus in osteoarthritic chondrocytes. This form of cell death is characterized by imbalances in iron and increased lipid peroxidation within osteoarthritic chondrocytes. Key antioxidant mechanisms, such as Glutathione Peroxidase 4 (GPX4) and the Nuclear Factor Erythroid 2-Related Factor 2 (NRF2) pathway, are vital in countering ferroptosis in osteoarthritic chondrocytes. This review collates recent findings on ferroptosis in osteoarthritic chondrocytes, emphasizing iron regulation, lipid peroxidation, and antioxidative responses. It also explores emerging therapeutics aimed at mitigating OA by targeting ferroptosis in chondrocytes.

Osteoarthritis (OA) is a degenerative musculoskeletal disease that significantly impacts the quality of life. Currently, no validated biomarkers for early detection of OA are defined. The possibility of discovering OA biomarkers is the focus of this study.

Human primary OA synovial cells (SVs), isolated from discarded joint tissue of patients with Kellgren & Lawrence score (KL) < 3, (mild/moderate) and KL ≥ 3 (severe), were characterized by FACS analysis. Through qRT-PCR and ELISA assays the inflammation, fibrosis status and the different miRNAs expression has been investigated. The role of miR-203a-3p and its precursors were evaluated through gain and loss of function study, IL-1β synoviocytes treatments and methylation analysis of miR203a promoter. The qRT-PCR analysis of miR203a-3p and pre-miR203a on plasma (isolated 24 h before surgery, 3 days and 1 month after surgery) and synovial fluid (recovered during the surgery) were done to support our in vitro data.

MiR203a-3p expression is inversely correlated with the aggressiveness of OA, modulating the expression of epithelial to mesenchymal transition (EMT) and pro-inflammatory factors, as well as regulating the expression of secreted protein acidic and rich in cysteine (SPARC) mRNA. Methylation analysis of the miR203a promoter and SVs IL-1β treatment's highlighted the impact of inflammation on miR203a-3p and pre-miR203a expression; as confirmed by both miRNAs detection in biological fluids derived from patients with severe OA.

Our preliminary results suggest that miR-203a-3p might be a potential candidate for staging OA progression and a new protective/predictive biomarker for synovial OA degeneration. Further studies are needed to validate its potential impact on OA.

Osteoarthritis (OA) is a chronic degenerative disease caused by various factors such as aging, obesity, trauma, and genetics. It is a challenging condition faced by orthopedic doctors in clinical practice and places a heavy burden on patients and their families. Currently, the treatment of OA primarily focuses on symptomatic relief and lacks ideal therapeutic methods. Resveratrol is a natural polyphenolic compound with anti-inflammatory and antioxidant properties, and in recent years, it has gained attention as a candidate drug for OA treatment. This article provides an overview of the research status on the role and mechanisms of resveratrol in treating OA. It has been found that resveratrol can prevent the development of OA by inhibiting inflammatory responses, protecting chondrocytes, maintaining cartilage homeostasis, promoting autophagy, and has shown certain therapeutic effects. This process may be related to the regulation of signaling pathways such as nuclear factor-kappa B (NF-κB), Toll-like receptor 4 (TLR4), and silent information regulator 1 (SIRT1). We summarize the current molecular mechanisms of resveratrol in treating OA, hoping to provide a reference for further research and application of resveratrol in OA treatment.

Osteoarthritis (OA) represents a chronic degenerative joint ailment characterized by the gradual breakdown of cartilage, inflicting substantial physical and economic burdens, especially among the elderly. Given the incomplete understanding of OA's pathogenesis, there is an increasing need to develop targeted therapeutic strategies and preventive measures. Conventional pharmaceutical interventions, such as non-steroidal anti-inflammatory drugs, steroids, and opioids, though effective, are often accompanied by notable adverse effects, thus emphasizing the urgency in seeking safer and more efficient therapeutic alternatives. The rapid evolution of nanotechnology has opened the door to various nanosystems for drug delivery, offering a promising avenue to mitigate these side effects. Of particular interest, recent research has shed light on the significant potential of polysaccharide-based nanosystems in the context of OA therapy, demonstrating their capability to counter inflammation, oxidative stress, regulate chondrocyte metabolism and proliferation, and protect cartilage. Therefore, in this review, we provide an in-depth examination of the role of polysaccharide nanosystems in OA, focusing on summarizing these findings based on different mechanisms of action. Furthermore, this review explores the application of combined polysaccharide nanosystems in OA, aiming to establish a foundation for the utilization of novel drug delivery nanoplatforms in OA treatment, ultimately expanding therapeutic options for this debilitating condition.

Dysregulated chondrocyte metabolism is an essential risk factor for osteoarthritis (OA) progression. Maintaining cartilage homeostasis represents a promising therapeutic strategy for the treatment of OA. However, no effective disease-modifying therapy is currently available to OA patients. To discover potential novel drugs for OA, we screened a small-molecule natural product drug library and identified deapi-platycodin D3 (D-PDD3), which was subsequently tested for its effect on extracellular matrix (ECM) properties and on OA progression. We found that D-PDD3 promoted the generation of ECM components in cultured chondrocytes and cartilage explants and that intra-articular injection of D-PDD3 delayed disease progression in a trauma-induced mouse model of OA. To uncover the underlying molecular mechanisms supporting these observed functions of D-PDD3, we explored the targets of D-PDD3 via screening approach integrating surface plasmon resonance with liquid chromatography-tandem mass spectrometry. The results suggested that D-PDD3 targeted tyrosine-protein phosphatase non-receptor type 1 (PTP1B), deletion of which restored chondrocyte homeostasis and markedly attenuated destabilization of the medial meniscus induced OA. Further cellular and molecular analyses showed that D-PDD3 maintained cartilage homeostasis by directly binding to PTP1B and consequently suppressing the PKM2/AMPK pathway. These findings demonstrated that D-PDD3 was a potential therapeutic drug for the treatment of OA and that PTP1B served as a protein target for the development of drugs to treat OA. This study provided significant insights into the development of therapeutics for OA treatment, which, in turn, helped to improve the quality of life of OA patients and to reduce the health and economic burden.

Background Nonsteroidal anti-inflammatory drugs (NSAIDs) are common drugs in patients with osteoarthritis (OA). NSAIDs are generally used at home by patients, without supervision, requiring proper knowledge and attitudes for correct practice. This study investigated the knowledge, attitude, and practice (KAP) of patients with OA toward NSAIDs. Methods This cross-sectional study enrolled patients with OA at the Qingpu Branch of Zhongshan Hospital of Fudan University between January and March 2024. The KAP scores and demographic information of respondents were collected through a self-designed questionnaire. Results There were 645 participants, with 579 (89.8%) over 45 years old and 394 (61.1%) females. The average scores for knowledge, attitude, and practice were 16.26 ± 3.79 (possible range: 0-24), 18.12 ± 1.99 (possible range: 5-35), and 29.20 ± 5.52 (possible range: 10-50), respectively. The structural equation model (SEM) found that for individuals currently using NSAIDs, the attitude had a direct effect on practice (β = 0.978, P < 0.001). For individuals not using NSAIDs, the attitude had a direct effect on practice (β = 0.936, P < 0.001). Conclusion This study suggested that adequate NSAID knowledge is the prerequisite for correct NSAID-related medical decisions, while attitude has a crucial intermediary effect. Healthcare professionals and society should strengthen education regarding the relevant knowledge of NSAIDs and guide the cultivation of positive attitudes toward NSAIDs.

Today, the prescription of tramadol in patients with osteoarthritis (OA) has increased significantly, which can be associated with serious consequences. Contradictory results have been reported regarding the association of tramadol versus codeine with the risk of all-cause mortality (ACM) and cardiovascular diseases (CVD).

This systematic review and meta-analysis aimed to evaluate, for the first time, the association of tramadol versus codeine with the risk of ACM and CVD in OA patients for the first time. We searched PubMed, Scopus, Embase, Web of sciences, and Google Scholar with specific keywords and mesh terms to find relevant studies until January 2024. Two independent researchers did the process of searching and screening articles. Cochran's Q and I2 tests evaluated the heterogeneity of the studies. Egger's test was used to evaluate the existence of publication bias.

Seven population-based cohort studies, matched by the propensity score method, including 1,939,293 participants, were reviewed. The study pooled results did not show a significant association between the prescriptions of tramadol versus codeine with increasing the risk of ACM in OA patients. (Hazard ratio (HR): 1.084, 95% confidence interval (95%) CI: 0.883, 1.286, P: 0.56) In addition, the prescription of tramadol versus codeine was not associated with an increased risk of CVD in OA. (HR: 1.025, 95% CI: 0.89, 1.16, P: 0.68, I2 = 37.8%) CONCLUSION: Our systematic review showed that tramadol prescription compared to codeine in OA patients was not associated with an increased risk of ACM and CVD.

Osteoarthritis (OA) is a degenerative disease with a high incidence worldwide. Most affected patients do not exhibit obvious discomfort symptoms or imaging findings until OA progresses, leading to irreversible destruction of articular cartilage and bone. Therefore, developing new diagnostic biomarkers that can reflect articular cartilage injury is crucial for the early diagnosis of OA. This study aims to explore biomarkers related to the immune microenvironment of OA, providing a new research direction for the early diagnosis and identification of risk factors for OA.

We screened and downloaded relevant data from the Gene Expression Omnibus (GEO) database, and the immune microenvironment-related genes (Imr-DEGs) were identified using the ImmPort data set by combining weighted coexpression analysis (WGCNA). Functional enrichment of GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) were conducted to explore the correlation of Imr-DEGs. A random forest machine learning model was constructed to analyze the characteristic genes of OA, and the diagnostic significance was determined by the Receiver Operating Characteristic Curve (ROC) curve, with external datasets used to verify the diagnostic ability. Different immune subtypes of OA were identified by unsupervised clustering, and the function of these subtypes was analyzed by gene set enrichment analysis (GSVA). The Drug-Gene Interaction Database was used to explore the relationship between characteristic genes and drugs.

Single sample gene set enrichment analysis (ssGSEA) revealed that 16 of 28 immune cell subsets in the dataset significantly differed between OA and normal groups. There were 26 Imr-DEGs identified by WGCNA, showing that functional enrichment was related to immune response. Using the random forest machine learning model algorithm, nine characteristic genes were obtained: BLNK (AUC = 0.809), CCL18 (AUC = 0.692), CD74 (AUC = 0.794), CSF1R (AUC = 0.835), RAC2 (AUC = 0.792), INSR (AUC = 0.765), IL11 (AUC = 0.662), IL18 (AUC = 0.699), and TLR7 (AUC = 0.807). A nomogram was constructed to predict the occurrence and development of OA, and the calibration curve confirmed the accuracy of these 9 genes in OA diagnosis.

This study identified characteristic genes related to the immune microenvironment in OA, providing new insight into the risk factors of OA.

This study investigated the protective effects of low fluid shear stress (FSS ≤ 2 dyn/cm²) against interleukin-1β (IL-1β)-induced chondrocyte apoptosis and explored the underlying molecular mechanisms.

Chondrocytes were cultured under four conditions: control, IL-1β stimulation, low FSS, and combined low FSS + IL-1β stimulation. Apoptosis was assessed using Hoechst staining and flow cytometry. Western blotting determined the expression of caspase-3 (CASP3), caspase-8 (CASP8), and NF-κB p65. Quantitative real-time PCR measured miR-143-3p expression. The roles of miR-143-3p and the extracellular signal-regulated kinase 5 (ERK5)/Krüppel-like factor 4 (KLF4) signaling pathway were further investigated using miR-143-3p mimics and inhibitors, an ERK5 inhibitor, and a KLF4 overexpression vector.

IL-1β induced significant chondrocyte apoptosis, which was markedly inhibited by low FSS. Mechanistically, low FSS suppressed miR-143-3p expression, thereby enhancing ERK5 signaling. This activated ERK5 subsequently upregulated KLF4 expression, further mitigating IL-1β-induced damage. Importantly, miR-143-3p overexpression under low FSS conditions exacerbated IL-1β-induced apoptosis, while miR-143-3p inhibition attenuated it. Consistent with this, ERK5 inhibition augmented IL-1β-induced apoptosis, whereas KLF4 overexpression suppressed it.

Low FSS protects chondrocytes from IL-1β-induced apoptosis by suppressing miR-143-3p and activating the ERK5/KLF4 signaling pathway. This study reveals a novel mechanism by which mechanical stimulation protects cartilage.

The complete circulating long non-coding RNAs (lncRNAs) signature of rheumatoid arthritis (RA) and osteoarthritis (OA) is still uncovered. The lncRNA integrin subunit beta 2 (ITGB2)-anti-sense RNA 1 (ITGB2-AS1) affects ITGB2 expression; however, there is a gap in knowledge regarding its expression and clinical usefulness in RA and OA. This study investigated the potential of serum ITGB2-AS1 as a novel diagnostic biomarker and its correlation with ITGB2 expression and its ligand intercellular adhesion molecule-1 (ICAM-1), disease activity, and severity in RA and primary knee OA patients.

Forty-three RA patients, 35 knee OA patients, and 22 healthy volunteers were included.

Compared with healthy controls, serum ITGB2-AS1 expression was upregulated in RA patients but wasn't significantly altered in knee OA patients, whereas serum ICAM-1 protein levels were elevated in both diseases. ITGB2-AS1 showed discriminative potential for RA versus controls (AUC = 0.772), while ICAM-1 displayed diagnostic potential for both RA and knee OA versus controls (AUC = 0.804, 0.914, respectively) in receiver-operating characteristic analysis. In the multivariate analysis, serum ITGB2-AS1 and ICAM-1 were associated with the risk of developing RA, while only ICAM-1 was associated with the risk of developing knee OA. A panel combining ITGB2-AS1 and ICAM-1 showed profound diagnostic power for RA (AUC = 0.9, sensitivity = 86.05%, and specificity = 91.67%). Interestingly, serum ITGB2-AS1 positively correlated with disease activity (DAS28) in RA patients and with ITGB2 mRNA expression in both diseases, while ICAM-1 positively correlated with ITGB2 expression in knee OA patients.

Our study portrays serum ITGB2-AS1 as a novel potential diagnostic biomarker of RA that correlates with disease activity. A predictive panel combining ITGB2-AS1 and ICAM-1 could have clinical utility in RA diagnosis. We also spotlight the association of ICAM-1 with knee OA diagnosis. The correlation of serum ITGB2-AS1 with ITGB2 expression in both diseases may be insightful for further mechanistic studies.

Globally, osteoarthritis (OA) is the most prevalent joint disease and is characterized by infiltration of M1 macrophages in the synovium, anabolic-catabolic imbalance of the extracellular matrix (ECM), increased articular shear force and overproduction of reactive oxygen species (ROS). Disease-modifying OA drugs are not yet available, and treatments for OA focus solely on reducing pain and inflammation and have limited therapeutic effect. Herein, we developed an injectable self-lubricating poly(N-acryloyl alaninamide) (PNAAA) hydrogel loaded with platelet lysate (PL) (termed "PNAAA@PL") for treating OA. Tribological and drug release tests revealed suitable lubrication properties and sustained release of bioactive factors in PNAAA@PL. In vitro experiments showed that PNAAA@PL alleviated interleukin-1β (IL-1β)-induced anabolic-catabolic imbalance of chondrocytes and repolarized pro-inflammatory M1 macrophages to the anti-inflammatory M2 phenotype via intracellular ROS scavenging. Additionally, the PNAAA@PL hydrogel enhanced the migratory capacity and chemotaxis ability of stem cells, which are essential for chondrogenesis. In vivo, the functionalized PNAAA@PL hydrogel acted like synovial fluid following intra-articular injection into a rat OA model with anterior cruciate ligament transection, ultimately attenuating cartilage degeneration and synovitis. According to molecular mechanism studies, PNAAA@PL repairs cartilage in the OA model by inhibiting the NF-ĸB pathway. Overall, this self-lubricating PNAAA@PL hydrogel offers a comprehensive strategy for preventing OA progression by engineering a biophysiochemical microenvironment to generate high-quality hyaline cartilage.

Oxidative stress and inflammation are key drivers of osteoarthritis (OA) pathogenesis and disease progression. Herein we report the synthesis of poly(p-coumaric) nanoparticles (PCA NPs) from p-courmaic acid (p-CA), a naturally occurring phytophenolic acid, to be a multifunctional and drug-free therapeutic for temporomandibular joint osteoarthritis (TMJOA). Compared to hyaluronic acid (HA) that is clinically given as viscosupplementation, PCA NPs exhibited long-term efficacy, superior anti-oxidant and anti-inflammatory properties in alleviating TMJOA and repairing the TMJ cartilage and subchondral bone in a rat model of TMJOA. Notably, TMJ repair mediated by PCA NPs could be attributed to their anti-oxidant and anti-inflammatory properties in enhancing cell proliferation and matrix synthesis, while reducing inflammation, oxidative stress, matrix degradation, and chondrocyte ferroptosis. Overall, our study demonstrates a multifunctional nanoparticle, synthesized from natural p-coumaric acid, that is stable and possess potent antioxidant, anti-inflammatory properties and ferroptosis inhibition, beneficial for treatment of TMJOA.

Osteoarthritis (OA) management remains challenging because of its intricate pathogenesis. Intra-articular injections of drugs, such as glucocorticoids and hyaluronic acid (HA), have certain limitations, including the risk of joint infection, pain, and swelling. Hydrogel-based therapeutic strategies have attracted considerable attention because of their enormous therapeutic potential. Herein, a supramolecular nanofiber hydrogel is developed using dexamethasone sodium phosphate (DexP) as a vector to deliver lentivirus-encoding hyaluronan synthase 2 (HAS2) (HAS2@DexP-Gel). During hydrogel degradation, HAS2 lentivirus and DexP molecules are slowly released. Intra-articular injection of HAS2@DexP-Gel promotes endogenous HA production and suppresses synovial inflammation. Additionally, HAS2@DexP-Gel reduces subchondral bone resorption in the anterior cruciate ligament transection-induced OA mice, attenuates cartilage degeneration, and delays OA progression. HAS2@DexP-Gel exhibited good biocompatibility both in vitro and in vivo. The therapeutic mechanisms of the HAS2@DexP-Gel are investigated using single-cell RNA sequencing. HAS2@DexP-Gel optimizes the microenvironment of the synovial tissue by modulating the proportion of synovial cell subpopulations and regulating the interactions between synovial fibroblasts and macrophages. The innovative nanofiber hydrogel, HAS2@DexP-Gel, effectively enhances endogenous HA production while reducing synovial inflammation. This comprehensive approach holds promise for improving joint function, alleviating pain, and slowing OA progression, thereby providing significant benefits to patients.