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

• DOI: 10.1038/nm.3668
• Publication Date: 2014-10-05T22:29:11Z
• 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
• Keywords: Ovariectomy; Acid Phosphatase; Cathepsin K; Becaplermin; Endothelial Cells; Neovascularization, Physiologic; Osteoclasts; Cell Count; Mesenchymal Stem Cells; 3. Good health; Isoenzymes; Mice, Inbred C57BL; Platelet Endothelial Cell Adhesion Molecule-1; Cell Movement; Osteogenesis; Culture Media, Conditioned; Focal Adhesion Protein-Tyrosine Kinases; Animals; Female; Femur; Phosphorylation

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.