Abstract
This study aimed to investigate the regulatory role of chordin-like 2 (CHRDL2) in the Th17/Treg balance and its impact on the progression of osteoarthritis (OA). We evaluated the levels of CHRDL2 and Th17/Treg-related cytokines, and the proportions of Th17 and Treg cells in peripheral blood from both healthy subjects and OA patients. An OA mouse model was established by destabilization of the medial meniscus (DMM) surgery, and lentivirus-mediated overexpression and knockdown of CHRDL2 were conducted. The clinical and pathological manifestations of the mice were assessed, and knee joint cartilage damage was evaluated using histological staining. Additionally, we examined the levels of Treg/Th17-related inflammatory factors and transcription factors in peripheral blood, as well as the Treg/Th17 ratio. In both OA patients and mice, CHRDL2 expression was downregulated, with a significant increase in Th17 cell proportion and IL-17 levels, while Treg cell proportion and IL-10 levels were significantly decreased. Overexpression of CHRDL2 significantly improved the clinical and pathological manifestations in OA mice, corrected the Th17/Treg imbalance, reduced IL-17 and RORγt levels, and increased IL-10 and Foxp3 levels. However, knockdown of CHRDL2 results in the opposite effect. This study demonstrates that CHRDL2 can suppress OA progression by regulating the Th17/Treg balance and may serve as a key therapeutic target for alleviating immune dysregulation in OA.