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PDGF-BB secreted by preosteoclasts induces angiogenesis during coupling with osteogenesis

2014; Nature Portfolio; Volume: 20; Issue: 11 Linguagem: Inglês

10.1038/nm.3668

1546-170X

Hui Xie, Zhuang Cui, Long Wang, Zhuying Xia, Yin Hu, Lingling Xian, Changjun Li, Liang Xie, Janet L. Crane, Mei Wan, Gehua Zhen, Qin Bian, Bin Yu, Weizhong Chang, Tao Qiu, Maureen Pickarski, Le T. Duong, Jolene J. Windle, Xiang‐Hang Luo, Ling‐Qing Yuan, Xu Cao,

Connective tissue disorders research

Preostoclasts secrete PDGF-BB to promote angiogenesis in the bone, promoting bone homeostasis and preventing bone loss in an osteoporosis model. 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 (CD31hiEmcnhi), couples angiogenesis and osteogenesis. Here, we found that platelet-derived growth factor-BB (PDGF-BB) secreted by preosteoclasts induces CD31hiEmcnhi 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 CD31hiEmcnhi 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 CD31hiEmcnhi 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 CD31hiEmcnhi 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.