Follistatin-like protein 1 (FSTL1) promotes chondrocyte expression of matrix metalloproteinase and inflammatory factors via the NF-κB pathway

J Cell Mol Med. 2019 Mar;23(3):2230-2237. doi: 10.1111/jcmm.14155. Epub 2019 Jan 15.

Abstract

Background: The expression of follistatin-like protein 1 (FSTL1) is closely associated with diseases of the musculoskeletal system. However, despite being a well characterized inflammatory mediator, the effects of FSTL1 on chondrocytes are not completely understood. In this study, we investigated the effects of FSTL1 on the expression of inflammatory and catabolic factors in rat chondrocytes.

Methods: Rat chondrocytes were treated directly with various concentrations of FSTL1 in vitro. The levels of matrix metalloproteinases (MMPs), inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, interleukin (IL)-1β, tumour necrosis factor (TNF)-α and IL-6 were measured by polymerase chain reaction, ELISA and Western blotting. In addition, activation of the nuclear factor kappa B (NF-κB) pathway was explored to identify potential regulatory mechanisms.

Results: Follistatin-like protein 1 directly increased the expression of MMP-1, MMP-13, iNOS, COX-2, IL-1β, TNF-α and IL-6 at both gene and protein level in a dose-dependent manner. Activation of NF- κB and phosphorylation of p65 were also promoted by FSTL1 stimulation.

Conclusions: Follistatin-like protein 1 exerts pro-inflammatory and catabolic effects on cultured chondrocytes via activation of the NF-κB signalling pathway. FSTL1 may therefore be a target in the treatment of OA.

Keywords: chondrocyte; follistatin-like protein 1; interleukin-1β; matrix metalloproteinase; nuclear factor kappa B; osteoarthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Cells, Cultured
  • Chondrocytes / drug effects*
  • Chondrocytes / metabolism
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Follistatin-Related Proteins / pharmacology*
  • Gene Expression / genetics
  • Inflammation Mediators / metabolism*
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Matrix Metalloproteinases / genetics
  • Matrix Metalloproteinases / metabolism
  • NF-kappa B / metabolism*
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • Rats
  • Signal Transduction / drug effects*
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Follistatin-Related Proteins
  • Inflammation Mediators
  • Interleukin-1beta
  • Interleukin-6
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2
  • Matrix Metalloproteinases

Associated data

  • GENBANK/NM_017008.4
  • GENBANK/NM_001134530.1
  • GENBANK/NM_133523
  • GENBANK/NM_133530
  • GENBANK/S67722
  • GENBANK/NM_012611.3
  • GENBANK/NM_031512
  • GENBANK/NM_012589
  • GENBANK/NM_012675