TITLE:
Chondroprotective Effect of Semaglutide in Osteoarthritis: Association with Macrophage Polarization
AUTHORS:
Ding Lei, Chunpeng Pang, Hongyi Huang, Zhongwen He, Lu Lu
KEYWORDS:
Osteoarthritis, Semaglutide, Macrophages, M1-M2 Polarization, Cartilage Repair
JOURNAL NAME:
Journal of Biosciences and Medicines,
Vol.14 No.5,
May
15,
2026
ABSTRACT: Objective: To investigate the chondroprotective effect of semaglutide in osteoarthritis (OA) and to observe whether this effect is associated with the regulation of synovial macrophage M1/M2 polarization. Methods: In vivo, a mouse OA model was established by destabilization of the medial meniscus (DMM) in C57BL/6J mice. Semaglutide (200 ng/mL) was administered via intraperitoneal (IP-Sema) or intra-articular (IA-Sema) injection. Synovial inflammation was evaluated by H&E staining (Krenn score), and cartilage degeneration was assessed by Safranin O-fast green staining (OARSI score). Immunohistochemistry was used to detect the expression of the M1 marker CD86 and the M2 marker CD206 in synovial tissues. In vitro, RAW264.7 macrophages were stimulated with LPS/IFN-γ to induce M1 polarization, followed by semaglutide treatment. Immunofluorescence staining was performed to assess the expression of CD86 and CD206. Results: Compared with the OA model group, semaglutide-treated groups exhibited significantly reduced synovial inflammation (decreased Krenn score) and delayed cartilage degeneration (decreased OARSI score), with the intra-articular injection showing superior efficacy. Immunohistochemistry revealed that semaglutide markedly decreased the number of CD86-positive cells (M1) and increased CD206-positive cells (M2) in synovial tissues. In vitro experiments confirmed that semaglutide directly inhibited LPS/IFN-γ-induced CD86 expression and promoted CD206 expression, indicating a shift from M1 to M2 macrophage phenotype. Conclusion: Semaglutide alleviates synovial inflammation and protects cartilage matrix in conjunction with an M1-to-M2 polarization shift. This study provides a new theoretical basis for the potential use of GLP-1 receptor agonists as a therapeutic option for OA.