Knee osteoarthritis (OA) is the most common cause of musculoskeletal pain and disability in the knee. Though traditionally thought a mechanical wear-and-tear disease, in recent years, knee OA as a low-grade, chronic inflammatory disease has been increasingly recognized. In this study, we examined the Treg responses in non-obese knee OA patients at different stages. Significantly elevated frequencies of CD4(+)CD25(+)Foxp3(+) Tregs were found in OA patients, while on the other hand, lower IL-10 secretion from Tregs in OA patients was observed. Importantly, this decrease in IL-10 was associated with reduced Tim-3 expression on Tregs. Although both Tim-3(-) and Tim3(+) Tregs could secrete IL-10, the majority of IL-10 was observed in Tim-3(+) Tregs. Reduction of Tim-3(+) Tregs in OA patients resulted in less IL-10-producing Tregs. Interestingly, the OA patients in more advanced stages showed further reductions in IL-10 and Tim-3 expression. In conclusion, our results revealed an immunoregulatory disorder in OA independent of obesity, and demonstrated a potential mechanism in establishing the proinflammatory status of OA patients.

Rheumatoid arthritis (RA) is characterized by a chronic inflammatory process that targets the synovial lining of diarthrodial joints. TIM-3 plays a key role in the negative regulation of the immune response. In this study, we investigated the expression of TIM-3 on CD4+ and CD8+ T cells from systemic (peripheral blood) and local (synovial fluid) perspectives of RA. Level of TIM-3+ cells from peripheral blood and synovial fluid of patients as well as peripheral blood of healthy controls was measured by flow cytometry. Results showed that TIM-3 expression was significantly increased in both CD4+ and CD8+ T cells in the peripheral blood of RA (p < 0.001 and p < 0.001, respectively). Furthermore, patients revealed even higher expression of TIM-3 in CD4+ and CD8+ T cells in synovial fluid than in peripheral blood. When comparing TIM-3 level with the severity of RA, we identified that the percentage of TIM-3 on both peripheral CD4+ and peripheral CD8+ T cells was negatively correlated with disease activity score 28 (DAS28) of the patients. Similarly, TIM-3 on synovial fluid CD4+ and CD8+ T cells also revealed inverse correlation with DAS28 of the cases. Our data demonstrate a negative correlation between TIM-3 and the disease progression of RA.

Level IV, retrospective case series.

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Objectives: To explore factors affecting the efficacy of Bernese periacetabular osteotomy for the treatment of hip dysplasia.Methods: A retrospective study was conducted on 44 patients with hip dysplasia who underwent Bernese periacetabular osteotomy with a modified Smith-Peterson approach between January 2017 and November 2019. Among them, 40 were women and four were men. The average age was 31.2 AE 9.4. Preoperative and postoperative imaging parameters were measured. The acetabular top tilt angle, lateral central edge angle, acetabular abduction angle, femoral head extrusion index, sphericity index of femoral head, Shenton line, Tonnis grade of osteoarthritis, joint congruency, p/a ratio, acetabular anteversion angle, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scale scores, and modified Harris hip score (MHHS) were observed. MHHS were divided into three clinically relevant categories: poor (<70 points), good (70-85 points), and excellent (86-91 points). Patient demographic data, as well as preoperative and postoperative radiographic parameters, were subjected to univariate logistic regression analysis. Multiple regression analysis was used to determine factors influencing postoperative MHHS. Results:The follow-up time was 1.0-3.9 years after surgery, with an average of 1.6 years. By the last follow-up, MHHS increased from 70 points before surgery to 91 points after surgery (P < 0.001), WOMAC pain score decreased from 4 points before surgery to 0 points after surgery (P < 0.001). WOMAC functional score decreased (Preoperative: 18.0 [4.0]; Postoperative: 4.0 [0], P = 0.004). Six patients had sensory disturbance of the lateral femoral cutaneous nerve, four of which recovered completely during follow-up. No other complications related to surgical approach, osteotomy, acetabular displacement, acetabular fixation, and postoperative stage were found. There was no significant vascular, nerve, or visceral injuries in any of the patients. On multiple regression analysis, the probability of the postoperative modified Harris hip score of a hip joint with a preoperative lateral center edge angle ≥4.5 being classified as excellent was six times that of angles <4.5 (Exp[β]: 6.249, 95% CI: 1.03-37.85, P = 0.046). Regression analysis of other factors found no significant correlation with postoperative functional scores. Conclusion:Overall functional scores post-PAO significantly improved, and pain symptoms were significantly reduced.Patients with a preoperative lateral center edge angle ≥4.5 had better joint function after surgery.

An aggressive proliferation of synoviocytes is the hallmark of rheumatoid arthritis (RA). Emerging evidence shows that inhibiting the NF-κB signaling pathway with 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] may be a therapeutic approach for controlling inflammatory diseases. In this study, we demonstrated the protective effects of three different 1,25(OH)2D3 concentration on adjuvant-induced arthritis (AA) rats through the NF-κB signaling pathway and their pro-apoptotic roles in cultured adjuvant-induced arthritis synoviocytes (AIASs). AA rats were prepared by injecting complete Freund's adjuvant and independently given daily intraperitoneal injection of 1,25(OH)2D3 at concentrations of 50, 100, and 300 ng/day/kg. Subsequently, AIASs were isolated from the inflamed joints of AA rats to test the effects of 1,25(OH)2D3 on AIASs in vitro. Intraperitoneal injection of 1,25-(OH)2D3 was found to induce a concentration- and time-dependent improvement in relieving the symptoms of AA. We found an increased paw withdrawal thermal latency (PWTL) in the affected paw of AA rats as the concentration of 1,25-(OH)2D3 increased. 1,25-(OH)2D3 treatment reduced levels of inflammatory factors in synovial tissues of AA rats. In the case of cultured AIASs, 1,25-(OH)2D3 was shown to inhibit cell proliferation and induce cell apoptosis in a concentration-dependent manner. Additionally, 1,25-(OH)2D3 inhibited the activation of the NF-κB signaling pathway. In conclusion, our study provides evidence emphasizing that 1,25(OH)2D3 has the potential to attenuate disease severity in RA potentially due to its contributory role in synoviocyte proliferation and apoptosis. The protective role of 1,25(OH)2D3 against RA depends on the NF-κB signaling pathway.

Osteoarthritis (OA) is the most common type of arthritis, in which T cell responses and cytokines may play critical roles in the development of the disease. TIM-3 may affect immune responses and is correlated with decreased expression of interferon gamma (INF-γ) in CD4+ T cells. In the current study, we investigated the association between polymorphisms in the TIM-3 gene and susceptibility to OA. Two polymorphisms in TIM-3, -574G/T and +4259T/G polymorphisms, were identified in OA cases and healthy donors by polymerase chain reaction-restriction fragment length polymorphism method. Data revealed that the prevalence of TIM-3 +4259T/G genotype was significantly elevated in OA patients than in the healthy donors after adjustment (Odds ratio [OR] = 2.67, 95% confidence interval [CI] 1.32-5.11, P < 0.001). Similarly, the TIM-3 +4259G allele presented a positive association with the risk of OA after adjustment (OR = 2.58, 95% CI 1.29-4.82, P = 0.003). The TIM-3 -574G/T polymorphism did not show any correlation with the disease. We further examined whether the two TIM-3 polymorphisms could affect INF-γ expression in CD4+ T cells. Data revealed that subjects carrying polymorphic +4259TG genotype had significantly higher mRNA and protein levels of INF-γ in CD4+ T cells compared to wild-type GG genotype (P < 0.001 and P < 0.01). These results indicated that TIM-3 polymorphism is associated with increased susceptibility to OA possibly by upregulating INF-γ expression in CD4+ T cells.