PDGF-BB Secreted by Preosteoclasts Induces Angiogenesis During Coupling with Osteogenesis

Overview

Journal Nat Med

Specialties General Medicine
Molecular Biology

Date 2014 Oct 6

PMID 25282358

Citations 419

Authors

Hui Xie

Zhuang Cui

Long Wang

Zhuying Xia

Yin Hu

Lingling Xian

Changjun Li

Liang Xie

Janet Crane

Mei Wan

Gehua Zhen

Qin Bian

Bin Yu

Weizhong Chang

Tao Qiu

Maureen Pickarski

Le Thi Duong

Jolene J Windle

Xianghang Luo

Eryuan Liao

Xu Cao

Affiliations

Soon will be listed here.

Abstract

Osteogenesis during bone modeling and remodeling is coupled with angiogenesis. A recent study showed that a specific vessel subtype, strongly positive for CD31 and endomucin (CD31(hi)Emcn(hi)), couples angiogenesis and osteogenesis. Here, we found that platelet-derived growth factor-BB (PDGF-BB) secreted by preosteoclasts induces CD31(hi)Emcn(hi) vessel formation during bone modeling and remodeling. Mice with depletion of PDGF-BB in the tartrate-resistant acid phosphatase-positive cell lineage show significantly lower trabecular and cortical bone mass, serum and bone marrow PDGF-BB concentrations, and fewer CD31(hi)Emcn(hi) vessels compared to wild-type mice. In the ovariectomy (OVX)-induced osteoporotic mouse model, serum and bone marrow levels of PDGF-BB and numbers of CD31(hi)Emcn(hi) vessels are significantly lower compared to sham-operated controls. Treatment with exogenous PDGF-BB or inhibition of cathepsin K to increase the number of preosteoclasts, and thus the endogenous levels of PDGF-BB, increases CD31(hi)Emcn(hi) vessel number and stimulates bone formation in OVX mice. Thus, pharmacotherapies that increase PDGF-BB secretion from preosteoclasts offer a new therapeutic target for treating osteoporosis by promoting angiogenesis and thus bone formation.

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