BAG3 protects chondrocytes against lumbar facet joint osteoarthritis by regulating autophagy and apoptosis

J Physiol Biochem. 2022 May;78(2):427-437. doi: 10.1007/s13105-021-00865-2. Epub 2022 Mar 7.

Abstract

Bcl2-associated athanogene3 (BAG3) protein, mainly induced by stressful stimuli, has been confirmed to participate in apoptosis and autophagy. In recent studies, BAG3 has gradually become a key molecule in tumors. However, the role of BAG3 in the progression of lumbar facet joint osteoarthritis (FJOA) and whether it can regulate chondrocyte apoptosis and autophagy are still unknown. In both human and FJOA rat models, we observed an upregulation of BAG3 and apoptosis and autophagy-related proteins compared with healthy tissues. Then, we established the chondrocytes injury model in vitro by using IL-1β to stimulate human SW1353 cells. Western blot analysis data showed significant expression of BAG3, apoptosis, and autophagy-related proteins in SW1353 cells. Finally, by knocking down and overexpressing BAG3, we discovered possible anti-apoptotic and autophagy-promoted effects of BAG3 in FJOA through various experimental methods. This study demonstrated that BAG3 actively participates in regulating chondrocyte apoptosis and autophagy in FJOA and may be a highly interesting target for pharmacological interventions.

Keywords: Apoptosis; Autophagy; BAG3; Lumbar facet joint.

MeSH terms

  • Adaptor Proteins, Signal Transducing* / genetics
  • Adaptor Proteins, Signal Transducing* / metabolism
  • Animals
  • Apoptosis
  • Apoptosis Regulatory Proteins* / genetics
  • Apoptosis Regulatory Proteins* / metabolism
  • Autophagy
  • Autophagy-Related Proteins / metabolism
  • Chondrocytes / metabolism
  • Humans
  • Osteoarthritis* / metabolism
  • Osteoarthritis* / pathology
  • Rats
  • Zygapophyseal Joint* / metabolism
  • Zygapophyseal Joint* / pathology

Substances

  • Adaptor Proteins, Signal Transducing
  • Apoptosis Regulatory Proteins
  • Autophagy-Related Proteins
  • BAG3 protein, human
  • BAG3 protein, rat