Conclusions
Bach1 deficiency reduces the severity of OA-like changes. This may be due to maintenance of cartilage homeostasis and joint health by antioxidant effects through HO-1 and downregulation of extracellular matrix degrading enzymes. These results suggest that inactivation of Bach1 is a novel target and signaling pathway in OA prevention.
Methods
HO-1 expression in Bach1 (-/-) mice was analyzed by real-time PCR, immunohistochemistry and immunoblotting. Knee joints from Bach1 (-/-) and wild-type mice with age-related OA and surgically-induced OA were evaluated by OA scoring systems. Levels of autophagy proteins and superoxide dismutase 2 (SOD2) were determined by immunohistochemistry. The relationship between HO-1 and the protective effects for OA was determined in chondrocytes treated with small interfering RNA (siRNA) targeting HO-1 gene.
Results
HO-1 expression decreased with aging in articular cartilages and menisci of mouse knees. Bach1 (-/-) mice showed reduced severity of age-related OA and surgically-induced OA compared with wild-type mice. Microtubule-associated protein 1 light chain 3 (LC3), autophagy marker, and SOD2 were increased in articular cartilage of Bach1 (-/-) mice compared with wild-type mice. Interleukin-1β (IL-1β) induced a significant increase in Adamts-5 in wild-type chondrocytes but not in Bach1(-/-) chondrocytes. The expression of SOD2 and the suppression of apoptosis in Bach1 (-/-) chondrocytes were mediated by HO-1. Conclusions: Bach1 deficiency reduces the severity of OA-like changes. This may be due to maintenance of cartilage homeostasis and joint health by antioxidant effects through HO-1 and downregulation of extracellular matrix degrading enzymes. These results suggest that inactivation of Bach1 is a novel target and signaling pathway in OA prevention.