Fibulin-5 protects the extracellular matrix of chondrocytes by inhibiting the Wnt/β-catenin signaling pathway and relieves osteoarthritis

Eur Rev Med Pharmacol Sci. 2020 May;24(10):5249-5258. doi: 10.26355/eurrev_202005_21307.

Abstract

Objective: Osteoarthritis (OA) is a common disease in the elderly and seriously affects the quality of life of patients. The purpose of this study was to explore the protective effect of Fibulin-5 on articular chondrocytes and its mechanism of action.

Patients and methods: Articular cartilage tissues from patients with OA and normal people were selected and tested for differences in Fibulin-5 expression. In addition, human chondrocytes were cultured, and the effects of Fibulin-5 on the extracellular matrix (ECM) of chondrocytes and the level of inflammation were examined by means of cell transfection and cytokine intervention. SKL2001, an agonist of the Wnt/β-catenin signaling pathway, was used to validate the mechanism of action of Fibulin-5 to protect chondrocytes.

Results: Fibulin-5 was lowly expressed in the cartilage tissue of patients with OA. Overexpression of Fibulin-5 significantly increased the expressions of ECM collagen II and aggrecan in chondrocytes, while decreasing the expressions of MMP-3 and MMP-13. In addition, Fibulin-5 reduced IL-1β-induced inflammation of chondrocytes, as well as expressions of IL-6, IL-8, and TNF-α. Overexpression of Fibulin-5 also reduced the activity of Wnt/β-catenin signaling pathway, and activation of Wnt/β-catenin signaling pathway attenuated the protective effects of Fibulin-5 on the ECM of chondrocytes.

Conclusions: Fibulin-5 can protect the ECM of chondrocytes and reduce the inflammatory response of chondrocytes by inhibiting the Wnt/β-catenin signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Chondrocytes / metabolism*
  • Extracellular Matrix / metabolism*
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / metabolism*
  • Humans
  • Osteoarthritis / metabolism*
  • Wnt Signaling Pathway*
  • beta Catenin / metabolism*

Substances

  • Extracellular Matrix Proteins
  • FBLN5 protein, human
  • beta Catenin