Osteoclast-Associated Receptor (OSCAR) Distribution in the Synovial Tissues of Patients with Active RA and TNF-α and RANKL Regulation of Expression by Osteoclasts In Vitro

Inflammation. 2017 Oct;40(5):1566-1575. doi: 10.1007/s10753-017-0597-2.

Abstract

Osteoclast-associated receptor (OSCAR) is a co-stimulatory receptor in osteoclastogenesis. Synovial tissues from active rheumatoid arthritis (RA) patients express higher levels of OSCAR compared with osteoarthritic and normal patients; however, the comparison of OSCAR levels in different regions of active RA synovium has not been reported. The regulation of OSCAR by TNF-α and receptor activator of NF kappa β ligand (RANKL) in pre-osteoclasts/osteoclasts in vitro is unclear. OSCAR and tartrate-resistant acid phosphatase (TRAP) expression levels did not differ between the cartilage pannus junction (CPJ) and non-CPJ regions in active RA. We demonstrate a similar pattern of OSCAR expression in the CPJ and non-CPJ synovial tissue from patients with active RA. OSCAR was associated with mononuclear cells in both the lining and sub-lining and endothelial cells (von Willebrand factor positive). Pre-osteoclasts (TRAP-positive cells) were present in the lining and sub-lining of both regions. OSCAR messenger RNA (mRNA) expression and release by pre-oscteoclasts/osteoclasts was modulated by RANKL with/without TNF-α in vitro. Osteoclast resorption on dentine slices was significantly greater with TNF-α pre-treatment and RANKL (10 ng/ml) than RANKL 10 or 50 ng/ml alone or RANKL 10 ng/ml with TNF-α given from day 3 post-RANKL. The lower levels of OSCAR mRNA expression corresponded with high osteoclast activity levels.

Keywords: OSCAR; cartilage pannus junction; osteoclast; rheumatoid arthritis.

MeSH terms

  • Arthritis, Rheumatoid / metabolism*
  • Endothelial Cells / chemistry
  • Humans
  • Leukocytes, Mononuclear / chemistry
  • Osteoclasts / metabolism*
  • RANK Ligand / physiology
  • RNA, Messenger / metabolism
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*
  • Synovial Membrane / chemistry*
  • Synovial Membrane / metabolism
  • Tartrate-Resistant Acid Phosphatase / metabolism
  • Tumor Necrosis Factor-alpha / physiology

Substances

  • OSCAR protein, human
  • RANK Ligand
  • RNA, Messenger
  • Receptors, Cell Surface
  • Tumor Necrosis Factor-alpha
  • ACP5 protein, human
  • Tartrate-Resistant Acid Phosphatase