Fargesin ameliorates osteoarthritis via macrophage reprogramming by downregulating MAPK and NF-κB pathways

作者：Jiansen Lu, Hongbo Zhang, Hongbo Zhang, Jianying Pan, Zhiqiang Hu, Liangliang Liu, Yanli Liu, Yu Xiao, Daozhang Cai, Daozhang Cai, Haiyan Zhang, Haiyan Zhang · 发表于：Arthritis Research & Therapy · 年份：2021 · DOI：10.1186/s13075-021-02512-z · 被引用次数：109 · 研究领域：Magnolia and Illicium research、Osteoarthritis Treatment and Mechanisms、Plant-derived Lignans Synthesis and Bioactivity

BACKGROUND: To investigate the role and regulatory mechanisms of fargesin, one of the main components of Magnolia fargesii, in macrophage reprogramming and crosstalk across cartilage and synovium during osteoarthritis (OA) development. METHODS: Ten-week-old male C57BL/6 mice were randomized and assigned to vehicle, collagenase-induced OA (CIOA), or CIOA with intra-articular fargesin treatment groups. Articular cartilage degeneration was evaluated using the Osteoarthritis Research Society International (OARSI) score. Immunostaining and western blot analyses were conducted to detect relative protein. Raw264.7 cells were treated with LPS or IL-4 to investigate the role of polarized macrophages. ADTC5 cells were treated with IL-1β and conditioned medium was collected to investigate the crosstalk between chondrocytes and macrophages. RESULTS: Fargesin attenuated articular cartilage degeneration and synovitis, resulting in substantially lower Osteoarthritis Research Society International (OARSI) and synovitis scores. In particular, significantly increased M2 polarization and decreased M1 polarization in synovial macrophages were found in fargesin-treated CIOA mice compared to controls. This was accompanied by downregulation of IL-6 and IL-1β and upregulation of IL-10 in serum. Conditioned medium (CM) from M1 macrophages treated with fargesin reduced the expression of matrix metalloproteinase-13, RUNX2, and type X collagen and increased Col2a1 and SOX9 in OA chondrocytes, but farges...