TY - JOUR T1 - Synovial macrophage M1 polarisation exacerbates experimental osteoarthritis partially through R-spondin-2 JF - Annals of the Rheumatic Diseases JO - Ann Rheum Dis SP - 1524 LP - 1534 DO - 10.1136/annrheumdis-2018-213450 VL - 77 IS - 10 AU - Haiyan Zhang AU - Chuangxin Lin AU - Chun Zeng AU - Zhenyu Wang AU - Hua Wang AU - Jiansen Lu AU - Xin Liu AU - Yan Shao AU - Chang Zhao AU - Jianying Pan AU - Song Xu AU - Yue Zhang AU - Denghui Xie AU - Daozhang Cai AU - Xiaochun Bai Y1 - 2018/10/01 UR - http://ard.bmj.com/content/77/10/1524.abstract N2 - Objectives To investigate the roles and regulatory mechanisms of synovial macrophages and their polarisation in the development of osteoarthritis (OA).Methods Synovial tissues from normal patients and patients with OA were collected. M1 or M2-polarised macrophages in synovial tissues of patients with OA and OA mice were analysed by immunofluorescence and immunohistochemical staining. Mice with tuberous sclerosis complex 1 (TSC1) or Rheb deletion specifically in the myeloid lineage were generated and subjected to intra-articular injection of collagenase (collagenase-induced osteoarthritis, CIOA) and destabilisation of the medial meniscus (DMM) surgery to induce OA. Cartilage damage and osteophyte size were measured by Osteoarthritis Research Society International score and micro-CT, respectively. mRNA sequencing was performed in M1 and control macrophages. Mice and ATDC5 cells were treated with R-spondin-2 (Rspo2) or anti-Rspo2 to investigate the role of Rspo2 in OA.Results M1 but not M2-polarised macrophages accumulated in human and mouse OA synovial tissue. TSC1 deletion in the myeloid lineage constitutively activated mechanistic target of rapamycin complex 1 (mTORC1), increased M1 polarisation in synovial macrophages and exacerbated experimental OA in both CIOA and DMM models, while Rheb deletion inhibited mTORC1, enhanced M2 polarisation and alleviated CIOA in mice. The results show that promoting the macrophage M1 polarisation leads to exacerbation of experimental OA partially through secretion of Rspo2 and activation of β-catenin signalling in chondrocytes.Conclusions Synovial macrophage M1 polarisation exacerbates experimental CIOA partially through Rspo2. M1 macrophages and Rspo2 are potential therapeutic targets for OA treatment. ER -