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On-line Access: 2023-09-17

Received: 2023-05-08

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Journal of Zhejiang University SCIENCE B

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Heme oxygenase 1 linked to inactivation of subchondral osteoclasts in osteoarthritis


Author(s):  Miao CHU, Guangdong CHEN, Kai CHEN, Pengfei ZHU, Zhen WANG, Zhonglai QIAN, Huaqiang TAO, Yaozeng XU, Dechun GENG

Affiliation(s):  Department of Orthopedics, The First Affiliated Hospital of Soochow University, No. 188 Shizi Street, Suzhou, Jiangsu, China; more

Corresponding email(s):  szgengdc@suda.edu.cn, 20224032009@stu.suda.edu.cn

Key Words:  Osteoclasts; Oxidative stress; Osteoarthritis; HMOX1; Carnosol


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Miao CHU, Guangdong CHEN, Kai CHEN, Pengfei ZHU, Zhen WANG, Zhonglai QIAN, Huaqiang TAO, Yaozeng XU, Dechun GENG. Heme oxygenase 1 linked to inactivation of subchondral osteoclasts in osteoarthritis[J]. Journal of Zhejiang University Science B,in press.Frontiers of Information Technology & Electronic Engineering,in press.https://doi.org/10.1631/jzus.B2300303

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year="in press",
publisher="Zhejiang University Press & Springer",
doi="https://doi.org/10.1631/jzus.B2300303"
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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 osteoclastic 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). GO and KEGG enrichment analyses demonstrated that chemical carcinogenesis, reactive oxygen species, 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, HOMX1, 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.

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