| Literature DB >> 32208385 |
Weiping Su1,2, Guanqiao Liu1,3, Xiaonan Liu1,3, Yangying Zhou4, Qi Sun1,5, Gehua Zhen1, Xiao Wang1, Yihe Hu2, Peisong Gao6, Shadpour Demehri7, Xu Cao1, Mei Wan1.
Abstract
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 (DMM), 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-β (PDGFR-β) signaling in pericytes for neo-vessel formation. Selective knockout of PDGF-BB in preosteoclasts attenuates subchondral bone angiogenesis and abrogates joint degeneration and subchondral innervation induced by DMM. 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.Entities:
Keywords: Angiogenesis; Bone Biology; Bone disease; Osteoarthritis; Osteoclast/osteoblast biology
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Year: 2020 PMID： 32208385 PMCID： PMC7205438 DOI： 10.1172/jci.insight.135446
Source DB: PubMed Journal: JCI Insight ISSN： 2379-3708