Inhibition of GAB2 expression has a protective effect on osteoarthritis:An in vitro and in vivo study

• Published in: Biochemical and biophysical research communications 2022-10, Vol.626, p.229-235
• Main Authors: Mo, Haokun, Yang, Siying, Chen, An-min
• Format: Article
• Language: English
• Subjects: Autophagy; cartilage; Chondrocytes; GAB2; MAPK; mice; mitogen-activated protein kinase; NF-κB; Osteoarthritis; pain; pathogenesis; protective effect; therapeutics
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2022.08.006

Osteoarthritis is a chronic age-related degenerative disease associated with varying degrees of pain and joint mobility disorders. Grb2-associated-Binding protein-2 (GAB2) is an intermediate molecule that plays a role downstream in a variety of signaling pathways, such as inflammatory signaling pathways. The role of GAB2 in the pathogenesis of OA has not been fully studied. In this study, we found that GAB2 expression was elevated in chondrocytes after constructing in vivo and in vitro models of OA. Inhibition of GAB2 by siRNA decreased the expression of MMP3, MMP13, iNOS, COX2, p62, and increased the expression of COL2, SOX9, ATG7, Beclin-1 and LC3II/LC3I. Furthermore, inhibition of GAB2 expression inhibited interleukin-1β (IL-1β) -induced mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB) signaling. In vivo studies, we found that reduced GAB2 expression effectively delayed cartilage destruction in a mouse model of OA induced by destabilisation of the medial meniscus (DMM). In conclusion, our study demonstrates that GAB2 is a potential therapeutic target for OA. •GAB2 expression increased in both in vitro and in vivo models of OA.•Knockdown of GAB2 alleviates IL-1β-induced dysregulation of anabolism and catabolism in chondrocytes.•Knockdown of GAB2 diminuts IL-1β-induced inflammation in chondrocytes.•Knockdown of GAB2 attenuates IL-1β-induced autophagy damage in chondrocytes.•Knockdown of GAB2 knockout inhibits IL-1β-induced activation of MAPK/NF-κB signaling pathway.