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JCI Insight. 2020 Mar 24. pii: 135446. doi: 10.1172/jci.insight.135446. [Epub ahead of print]

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

Author information

1
Department of Orthopaedic Surgery, The Johns Hopkins University School of Medicine, Baltimore, United States of America.
2
Department of Oncology, Xiangya Hospital, Central South University, Changsha, China.
3
Department of Orthopaedic Surgery, The Xiangya Hospital of Central South University, Changsha, China.
4
Johns Hopkins Asthma & Allergy Center, Johns Hopkins University School of Medicine, Baltimore, United States of America.
5
Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, United States of America.

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 (PDGFRβ) 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 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.

KEYWORDS:

Angiogenesis; Bone Biology; Bone disease; Osteoarthritis; Osteoclast/osteoblast biology

PMID:
32208385
DOI:
10.1172/jci.insight.135446
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