Heme oxygenase 1 linked to inactivation of subchondral osteoclasts in osteoarthritis

Chu Miao; Chen Guangdong; Chen Kai; Zhu Pengfei; Wang Zhen; Qian Zhonglai; Tao Huaqiang; XU Yaozeng; Geng Dechun

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Heme oxygenase 1 linked to inactivation of subchondral osteoclasts in osteoarthritis

Author: CHU MIAO ^{1
,

2} ; CHEN GUANGDONG ; CHEN KAI ; ZHU PENGFEI ; WANG ZHEN ; QIAN ZHONGLAI ; TAO HUAQIANG ; XU YAOZENG ; GENG DECHUN
Author Information

1. Department of Orthopedics,the First Affiliated Hospital of Soochow University,Suzhou 215006,China
2. Department of Orthopedics,Yixing People's Hospital,Yixing 214200,China
Keywords: Osteoclast; Oxidative stress; Osteoarthritis(OA); Heme oxygenase 1(HMOX1); Carnosol
From: Journal of Zhejiang University. Science. B 2024;25(6):513-528,中插3-中插9
CountryChina
Language:Chinese
Abstract: Osteoarthritis(OA)is a chronic progressive osteoarthropathy in the elderly.Osteoclast activation plays a crucial role in the occurrence of subchondral bone loss in early OA.However,the specific mechanism of osteoclast differentiation in OA remains unclear.In our study,gene expression profiles related to OA disease progression and osteoclast activation were screened from the Gene Expression Omnibus(GEO)repository.GEO2R and Funrich analysis tools were employed to find differentially expressed genes(DEGs).Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses demonstrated that chemical carcinogenesis,reactive oxygen species(ROS),and response to oxidative stress were mainly involved in osteoclast differentiation in OA subchondral bone.Furthermore,fourteen DEGs that are associated with oxidative stress were identified.The first ranked differential gene,heme oxygenase 1(HMOX1),was selected for further validation.Related results showed that osteoclast activation in the pathogenesis of OA subchondral bone is accompanied by the downregulation of HMOX1.Carnosol was revealed to inhibit osteoclastogenesis by targeting HMOX1 and upregulating the expression of antioxidant protein in vitro.Meanwhile,carnosol was found to alleviate the severity of OA by inhibiting the activation of subchondral osteoclasts in vivo.Our research indicated that the activation of osteoclasts due to subchondral bone redox dysplasia may serve as a significant pathway for the advancement of OA.Targeting HMOX1 in subchondral osteoclasts may offer novel insights for the treatment of early OA.