Maintaining hypoxia environment of subchondral bone alleviates osteoarthritis progression

Author:

Zhang Hao123ORCID,Wang Lipeng2ORCID,Cui Jin12ORCID,Wang Sicheng24ORCID,Han Yafei2ORCID,Shao Hongda5ORCID,Wang Cheng5ORCID,Hu Yan23ORCID,Li Xiaoqun16ORCID,Zhou Qirong1ORCID,Guo Jiawei12ORCID,Zhuang Xinchen1ORCID,Sheng Shihao1ORCID,Zhang Tao1ORCID,Zhou Dongyang2ORCID,Chen Jiao2ORCID,Wang Fuxiao2ORCID,Gao Qianmin2ORCID,Jing Yingying2ORCID,Chen Xiao13ORCID,Su Jiacan123ORCID

Affiliation:

1. Department of Orthopedics, Shanghai Changhai Hospital, Naval Medical University, Shanghai 200433, China.

2. Institute of Translational Medicine, Shanghai University, Shanghai 200444, China.

3. Department of Orthopedic, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.

4. Department of Orthopedics, Shanghai Zhongye Hospital, Shanghai 200941, China.

5. Department of Nuclear Medicine, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.

6. Department of Orthopedics, No. 929 Hospital, Naval Medical University, Shanghai 200433, China.

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 ( Lcp1 ) knockout mice to suppress subchondral osteoclasts in a mice OA model with anterior cruciate ligament transection (ACLT), and Lcp1 −/− 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. Lcp1 knockout impeded angiogenesis, which maintained hypoxia environment in joints and delayed the OA progression. Stabilization of HIF-1α delayed cartilage degeneration, and knockdown of Hif1a abolished the protective effects of Lcp1 knockout. Last, we showed that Oroxylin A, an Lcp1- encoded protein l -plastin (LPL) inhibitor, could alleviate OA progression. In conclusion, maintaining hypoxic environment is an attractive strategy for OA treatment.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

全球学者库

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"全球学者库"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前全球学者库共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2023 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3