CEMIP (KIAA1199) regulates inflammation, hyperplasia and fibrosis in osteoarthritis synovial membrane

Cell Mol Life Sci. 2022 Apr 27;79(5):260. doi: 10.1007/s00018-022-04282-6.

Abstract

Osteoarthritis (OA) synovial membrane is mainly characterized by low-grade inflammation, hyperplasia with increased cell proliferation and fibrosis. We previously underscored a critical role for CEMIP in fibrosis of OA cartilage. However, its role in OA synovial membrane remains unknown. An in vitro model with fibroblast-like synoviocytes from OA patients and an in vivo model with collagenase-induced OA mice were used to evaluate CEMIP-silencing effects on inflammation, hyperplasia and fibrosis. Our results showed that i. CEMIP expression was increased in human and mouse inflamed synovial membrane; ii. CEMIP regulated the inflammatory response pathway and inflammatory cytokines production in vitro and in vivo; iii. CEMIP induced epithelial to mesenchymal transition pathway and fibrotic markers in vitro and in vivo; iv. CEMIP increased cell proliferation and synovial hyperplasia; v. CEMIP expression was increased by inflammatory cytokines and by TGF-β signaling; vi. anti-fibrotic drugs decreased CEMIP expression. All these findings highlighted the central role of CEMIP in OA synovial membrane development and underscored that targeting CEMIP could be a new therapeutic approach.

Keywords: CEMIP; Fibrosis; Hybid; Inflammation; KIAA1199; Osteoarthritis; Synovitis.

MeSH terms

  • Animals
  • Cytokines / metabolism
  • Epithelial-Mesenchymal Transition*
  • Fibrosis
  • Humans
  • Hyaluronoglucosaminidase* / metabolism
  • Hyperplasia / metabolism
  • Inflammation / pathology
  • Mice
  • Osteoarthritis* / metabolism
  • Synovial Membrane / metabolism
  • Synovial Membrane / pathology

Substances

  • Cytokines
  • CEMIP protein, human
  • Cemip protein, mouse
  • Hyaluronoglucosaminidase