S100B regulates inflammatory response during osteoarthritis via fibroblast growth factor receptor 1 signaling

Mol Med Rep. 2018 Dec;18(6):4855-4864. doi: 10.3892/mmr.2018.9523. Epub 2018 Oct 1.

Abstract

The present study aimed to investigate the role of S100B in the inflammation process during osteoarthritis (OA). OA cartilage samples were collected for S100B expression analysis. S100B expression levels were significantly increased in patients with OA compared with the Controls (1.28±0.66 vs. 0.42±0.31; P=0.01) and were determined to be correlated with TNF‑α (r=0.42; P=0.04) and IL‑1β (r=0.73; P=0.001) expression levels. Orthopedic casting tape was used to immobilize the right knee at 180˚ extension of adult female New Zealand white rabbits for 4 weeks to establish an OA model. Cartilage specimens from the medial femoral condyle of these rabbits were used for histological confirmation and immunohistochemical analyses, whereas synovial fluid was used in ELISA assays for tumor necrosis factor (TNF)‑α and interleukin (IL)‑1β expression levels. Human synovial fibroblasts from the knee synovial tissues of normal patients with traumatic injury were transfected with S100B overexpression and knockdown plasmids and subjected to lipopolysaccharide (LPS) stimulation; subsequently, TNF‑α and IL‑1β expression levels in conditioned medium were determined by ELISA; S100B overexpression and knockdown significantly increased and decreased the TNF‑α and IL‑1β expression levels, respectively. Increased TNF‑α (573.3±15.4 vs. 102.6±8.7 pg) and IL‑1β (378.6±7.2 vs. 170.1±5.8 pg) expression levels were detected in OA model rabbits compared with the Control rabbits. Additionally, S100B, fibroblast growth factor (FGF)‑1 and FGF receptor (FGFR)‑1 mRNA and protein expression levels were increased in OA model rabbits compared with the Control group. FGFR1 knockdown significantly decreased TNF‑α and IL‑1β expression levels in LPS‑stimulated S100B‑overexpressing human synovial fibroblasts. S100B is involved in FGFR1 signaling‑mediated inflammatory response during OA, which may be considered as a potential therapeutic target.

Keywords: S100B; osteoarthritis; fibroblast growth factorreceptor 1; inflammation.

MeSH terms

  • Aged
  • Animals
  • Case-Control Studies
  • Female
  • Fibroblasts / metabolism
  • Gene Expression
  • Humans
  • Immunohistochemistry
  • Male
  • Osteoarthritis / diagnosis
  • Osteoarthritis / genetics
  • Osteoarthritis / metabolism*
  • Rabbits
  • Receptor, Fibroblast Growth Factor, Type 1 / metabolism*
  • S100 Calcium Binding Protein beta Subunit / genetics
  • S100 Calcium Binding Protein beta Subunit / metabolism*
  • Severity of Illness Index
  • Signal Transduction*
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • S100 Calcium Binding Protein beta Subunit
  • S100B protein, human
  • Tumor Necrosis Factor-alpha
  • Receptor, Fibroblast Growth Factor, Type 1