Background: Osteoarthritis (OA) pathogenesis involves age-related immune dysregulation, yet non-invasive diagnostic tools and mechanistic insights remain limited. Methods: We integrated transcriptomic profiling of four OA-affected joint tissues with machine learning to identify potential peripheral blood biomarkers. Weighted gene co-expression network analysis was employed to explore gene modules and pathways associated with OA. Single-cell RNA sequencing was performed on 217 983 joint cells to delineate B cell differentiation trajectories. Flow cytometry was used to validate age-associated B cell imbalances in peripheral blood. Results: We identified five peripheral blood biomarkers: MAPK1, MAP3K8, ING1, LDLR, and NUP153 in distinguishing OA patients from controls (the area under the curve [AUC] = 0.966). Importantly, these markers exhibited age-specific expression profiles; ING1, NUP153, and MAP3K8 were elevated, while MAPK1 was reduced in elderly compared to younger OA patients. A refined predictive model based on these age-specific markers demonstrated superior performance specifically for elderly Knee OA (KOA, AUC: 0.8 vs. 0.7 for younger KOA). These biomarkers correlated with immune cell infiltration and inflammatory cytokines. In osteoarthritic joint tissues, B cells predominantly originated from subchondral bone and synovium. Single-cell analysis identified age-specific B cell differentiation patterns, with elderly KOA patients enriched in an activated B cell cluster (C1). Furthermore, B cells from elderly KOA patients showed altered energy metabolism and increased proportions in peripheral blood, and functionally promoted chondrocyte damage. Conclusion: Our findings establish a novel blood-based diagnostic framework for OA and uncover aging-driven B cell remodeling as a key contributor to elderly OA pathogenesis. These findings offer non-invasive diagnostics and immunomodulatory targets for age-specific OA therapy.

The ongoing debate regarding the excision of the infrapatellar fat pad (IPFP) during total knee arthroplasty (TKA) remains a contentious issue, with established parameters for IPFP management still lacking. Excessive resection of IPFP tissue may lead to patellar tendon (PT) shortening and reduced mobility of the knee joint. This study aims to evaluate whether the resection of pathologically altered IPFP tissue during TKA affects knee joint function and PT dimensions. A total of 100 patients with end-stage knee osteoarthritis (KOA) who successfully underwent their first TKA were randomly assigned to two groups: one group received resection of the pathologically altered IPFP tissue, while the other group underwent complete resection of all IPFP tissue. The excised IPFP specimens were subjected to pathological and immunohistochemical analysis. Patients underwent X-ray and MRI assessments prior to surgery, as well as at 6 weeks and 6 months postoperatively; additionally, the Numeric Rating Scale (NRS), Knee Injury and Osteoarthritis Outcome Scale (KOOS), and Oxford Knee Score (OKS) were utilized for evaluation. Furthermore, patellar tendon length and thickness were assessed. Histological examination of the IPFP tissue from patients with KOA revealed that not all IPFP specimens exhibited lesions under hematoxylin and eosin (HE) staining and immunohistochemical analysis, with lesion areas predominantly localized near the synovium. There was no significant difference in the NRS scores between the two patient groups at 6 weeks or 6 months postoperatively (Mann-Whitney test, P = 0.391; P = 0.055). However, a significant difference was observed in both KOOS and OKS between the two groups at 6 months after surgery (Mann-Whitney test, P < 0.05). Sonographic evaluation of patellar tendon parameters indicated a significant difference in PT thickness between the two groups only at 6 weeks postoperatively (Mann-Whitney test, P < 0.05). This study demonstrated that the resection of pathologically altered IPFP tissue during TKA in patients with end-stage KOA can significantly enhance early postoperative knee joint mobility, improve life satisfaction, and mitigate the impact on PT structure.

Previous research has demonstrated a robust association between osteoarthritis (OA) and psoriasis. Notably, a significant proportion of psoriasis patients exhibit symptoms of arthritis, particularly psoriatic arthritis. However, a definitive causal relationship between psoriasis, psoriatic arthritis and OA remains to be established. This study aimed to elucidate the causal relationship between psoriasis, psoriatic arthritis, and osteoarthritis using a 2-sample Mendelian randomization approach. The causal relationship between psoriasis, psoriatic arthritis and OA was rigorously investigated using a 2-sample Mendelian Randomization (MR) approach. Instrumental variables pertinent to psoriasis, psoriatic arthritis and 4 distinct types of OA (knee osteoarthritis (KOA), hand osteoarthritis (HOA), total knee replacement (TKR), and total hip replacement (THR)) were sourced from extensive, published genome-wide association studies (GWAS). To estimate the causal effects, methodologies such as inverse variance weighting (IVW), MR-Egger, and weighted median estimation (WM) were employed. Mendelian Randomization analysis suggested a potential causal effect of psoriasis on osteoarthritis (OA). For hand OA (HOA), the P value was .381 (OR = 0.28); for knee OA (KOA), the P value was .725 (OR = 1.46); for TKR, the P value was .488 (OR = 0.274); and for THR, the P value was .454 (OR = 0.216). Furthermore, we explored the causality of psoriatic arthritis on OA. For HOA, the P value was .478 (OR = 0.0095); for KOA, the P value was .835 (OR = 0.345); for THR, the P value was .807 (OR = 0.120); and for TKR, the P value was .860 (OR = 0.190). Our findings indicate that there is no evidence of a causal connection between psoriasis or psoriatic arthritis and OA, suggesting that while psoriasis may contribute to arthritis, it does not influence OA development.

Observational studies have demonstrated an association between hypertension and frozen shoulder (FS). However, there is still a lack of clarity about their possible causal relationship. This study aimed to explore whether a genetic relationship exists between hypertension and FS bidirectional through 2-sample Mendelian randomization (MR) analysis. In this study, we investigated the following using data from genome-wide association studies. Exposure-related genetic variants that are independent of each other, were rigorously screened for use as instrumental variables (IVs). To investigate the causal connection, we performed the bidirectional 2-sample MR analysis using these IVs. Inverse-variance weighted (IVW) analysis was the primary method used to analyze the data and augmented by 4 additional analyses: MR-Egger, simple model, weighted model, and weighted median. Additionally, sensitivity analyses were performed to evaluate the impact of heterogeneity and pleiotropy on the results of our study, by comparing different models and tests to ensure robustness. The result of IVW analysis indicated a negative association between hypertension and FS (OR: 0.923, 95% confidence area (CI): 0.863–0.986, P-value was .018); Conversely, no significant effect of FS on developing hypertension cloud be observed (OR: 0.867, 95% CI: 0.746–1.008, P-value was .063). The stability of these results was verified through sensitivity analyses. Our research revealed a negative association between hypertension and FS; however, reverse MR analysis did not demonstrate a causal effect of FS on hypertension. There was no reciprocal genetic causation between these 2 conditions.