Roles and Mechanisms of Irisin in Attenuating Pathological Features of Osteoarthritis

Xiangfen Li, Xiaofang Zhu, Hongle Wu, Thomas E. Van Dyke, Xiaoyang Xu, Elise F. Morgan, Wenyu Fu, Chuanju Liu, Qisheng Tu, Dingming Huang, Jake Chen

Research output: Contribution to journalArticlepeer-review

Abstract

To investigate the effects and mechanisms of irisin, a newly discovered myokine, in cartilage development, osteoarthritis (OA) pathophysiology and its therapeutic potential for treating OA we applied the following five strategical analyses using (1) murine joint tissues at different developmental stages; (2) human normal and OA pathological tissue samples; (3) experimental OA mouse model; (4) irisin gene knockout (KO) and knock in (KI) mouse lines and their cartilage cells; (5) in vitro mechanistic experiments. We found that Irisin was involved in all stages of cartilage development. Both human and mouse OA tissues showed a decreased expression of irisin. Intra-articular injection of irisin attenuated ACLT-induced OA progression. Irisin knockout mice developed severe OA while irisin overexpression in both irisin KI mice and intraarticular injection of irisin protein attenuated OA progression. Irisin inhibited inflammation and promoted anabolism in chondrogenic ADTC5 cells. Proliferative potential of primary chondrocytes from KI mice was found to be enhanced, while KO mice showed an inhibition under normal or inflammatory conditions. The primary chondrocytes from irisin KI mice showed reduced expression of inflammatory factors and the chondrocytes isolated from KO mice showed an opposite pattern. In conclusion, it is the first time to show that irisin is involved in cartilage development and OA pathogenesis. Irisin has the potential to ameliorate OA progression by decreasing cartilage degradation and inhibiting inflammation, which could lead to the development of a novel therapeutic target for treating bone and cartilage disorders including osteoarthritis.

Original languageEnglish (US)
Article number703670
JournalFrontiers in Cell and Developmental Biology
Volume9
DOIs
StatePublished - Sep 28 2021

All Science Journal Classification (ASJC) codes

  • Developmental Biology
  • Cell Biology

Keywords

  • cartilage
  • gene knockout
  • irisin
  • osteoarthritis
  • transgenics

Fingerprint

Dive into the research topics of 'Roles and Mechanisms of Irisin in Attenuating Pathological Features of Osteoarthritis'. Together they form a unique fingerprint.

Cite this