Leptin promotes obesity‑related osteoarthritis progression via CD44/JAK2/STAT3 axis‑mediated chondrocyte apoptosis.

Abstract

Osteoarthritis (OA), especially obesity‑related OA, is a common joint disease in which leptin serves a notable role; however, the specific mechanism by which leptin promotes obesity‑related OA progression remains unclear. In the present study, human cartilage samples confirmed the association between leptin and obesity‑related OA. The Gene Expression Omnibus dataset GSE85785 was analyzed in R. Differential gene expression was screened using reverse transcription‑quantitative PCR. The protein levels of CD44, apoptosis‑related proteins and Janus kinase 2 (JAK2)/STAT3 pathway‑related proteins were examined using western blotting. Chondrocyte apoptosis was assessed using TUNEL staining and flow cytometry. Cartilage degeneration was evaluated using H&E and Safranin O‑Fast Green staining. Immunofluorescence staining and immunohistochemistry were employed to detect relevant proteins (Leptin, CD44, STAT3). The results from the present study demonstrated that leptin stimulation markedly upregulated CD44 expression, activated the JAK2/STAT3 signaling pathway and induced apoptosis in C28/I2 chondrocytes. Furthermore, the AG490 inhibitor markedly suppressed apoptosis. CD44 knockdown inhibited leptin‑induced activation of the JAK2/STAT3 pathway and apoptosis in C28/I2 chondrocytes, whereas CD44 overexpression activated JAK2/STAT3 signaling and promoted apoptosis. Animal experiments further confirmed that leptin administration induced OA, as shown by histological analysis (H&E and Safranin O‑Fast Green staining) revealing cartilage degeneration and matrix loss and TUNEL staining revealed increased chondrocyte apoptosis in leptin‑treated rats. In summary, the present study identified a novel mechanism by which leptin induced chondrocyte apoptosis and promoted OA through activation of the CD44‑mediated JAK2/STAT3 pathway.