Angiogenesis stimulated by elevated PDGF-BB in subchondral bone contributes to osteoarthritis development

被引：226

作者：

Su, Weiping ^{[1
,2
]}

Liu, Guanqiao ^{[1
,3
]}

Liu, Xiaonan ^{[1
,3
]}

Zhou, Yangying ^{[4
]}

Sun, Qi ^{[1
,5
]}

Zhen, Gehua ^{[1
]}

Wang, Xiao ^{[1
]}

Hu, Yihe ^{[2
]}

Gao, Peisong ^{[6
]}

Demehri, Shadpour ^{[7
]}

Cao, Xu ^{[1
]}

Wan, Mei ^{[1
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Dept Orthopaed Surg, Baltimore, MD USA

[2] Cent South Univ, Dept Orthopaed Surg, Xiangya Hosp, Changsha, Peoples R China

[3] Southern Med Univ, Nanfang Hosp, Dept Orthopaed & Traumatol, Guangzhou, Peoples R China

[4] Cent South Univ, Dept Oncol, Xiangya Hosp, Changsha, Peoples R China

[5] Tongji Univ, Shanghai Peoples Hosp 10, Dept Orthopaed, Sch Med, Shanghai, Peoples R China

[6] Johns Hopkins Univ, Sch Med, Johns Hopkins Asthma & Allergy Ctr, Baltimore, MD USA

[7] Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA

来源：

JCI INSIGHT | 2020年 / 5卷 / 08期

基金：

美国国家卫生研究院;

关键词：

OSTEOCHONDRAL JUNCTION; COLLAGEN METABOLISM; GROWTH-FACTORS; NERVE GROWTH; CARTILAGE; OSTEOCLAST; BIOLOGY; BETA; OSTEOGENESIS; PROGRESSION;

D O I：

10.1172/jci.insight.135446

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

100103 [病原生物学]; 100218 [急诊医学];

摘要：

Increased subchondral bone angiogenesis with blood vessels breaching the tidemark into the avascular cartilage is a diagnostic feature of human osteoarthritis. However, the mechanisms that initiate subchondral bone angiogenesis remain unclear. We show that abnormally increased platelet-derived growth factor-BB (PDGF-BB) secretion by mononuclear preosteoclasts induces subchondral bone angiogenesis, contributing to osteoarthritis development. In mice after destabilization of the medial meniscus (EIMM), aberrant joint subchondral bone angiogenesis developed during an early stage of osteoarthritis, before articular cartilage damage occurred. Mononuclear preosteoclasts in subchondral bone secrete excessive amounts of PDGF-BB, which activates platelet-derived growth factor receptor-beta (PDGFR-beta) signaling in pericytes for neovessel formation. Selective knockout of PDGF-BB in preosteoclasts attenuates subchondral bone angiogenesis and abrogates joint degeneration and subchondral innervation induced by OMM. Transgenic mice that express PDGF-BB in preosteoclasts recapitulate pathological subchondral bone angiogenesis and develop joint degeneration and subchondral innervation spontaneously. Our study provides the first evidence to our knowledge that PDGF-BB derived from preosteoclasts is a key driver of pathological subchondral bone angiogenesis during osteoarthritis development and offers a new avenue for developing early treatments for this disease.

引用

页数：16

共 63 条

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