Maintaining Hypoxia Environment of Subchondral Bone Alleviates Osteoarthritis Progression

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2023 Apr 5

PMID 37018403

Authors

Hao Zhang

Lipeng Wang

Jin Cui

Sicheng Wang

Yafei Han

Hongda Shao

Cheng Wang

Yan Hu

Xiaoqun Li

Qirong Zhou

Jiawei Guo

Xinchen Zhuang

Shihao Sheng

Tao Zhang

Dongyang Zhou

Jiao Chen

Fuxiao Wang

Qianmin Gao

Yingying Jing

Xiao Chen

Jiacan Su

Affiliations

Soon will be listed here.

Abstract

Abnormal subchondral bone remodeling featured by overactivated osteoclastogenesis leads to articular cartilage degeneration and osteoarthritis (OA) progression, but the mechanism is unclear. We used lymphocyte cytosolic protein 1 () knockout mice to suppress subchondral osteoclasts in a mice OA model with anterior cruciate ligament transection (ACLT), and mice showed decreased bone remodeling in subchondral bone and retarded cartilage degeneration. For mechanisms, the activated osteoclasts in subchondral bone induced type-H vessels and elevated oxygen concentration, which ubiquitylated hypoxia-inducible factor 1 alpha subunit (HIF-1α) in chondrocytes and led to cartilage degeneration. knockout impeded angiogenesis, which maintained hypoxia environment in joints and delayed the OA progression. Stabilization of HIF-1α delayed cartilage degeneration, and knockdown of abolished the protective effects of knockout. Last, we showed that Oroxylin A, an encoded protein l-plastin (LPL) inhibitor, could alleviate OA progression. In conclusion, maintaining hypoxic environment is an attractive strategy for OA treatment.

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