Hui Xie 1 , 2 , Zhuang Cui 1 , 3 , Long Wang 1 , 4 , Zhuying Xia 1 , 2 , Yin Hu 1 , 2 , Lingling Xian 1 , Changjun Li 1 , Liang Xie 1 , Janet Crane 1 , Mei Wan 1 , Gehua Zhen 1 , Qin Bian 1 , Bin Yu 3 , Weizhong Chang 1 , Tao Qiu 1 , Maureen Pickarski 5 , Le Thi Duong 5 , Jolene J. Windle 6 , Xianghang Luo 2 , * , Eryuan Liao 2 , * , Xu Cao 1 , *
05 October 2014
Osteogenesis during bone modeling and remodeling is coupled with angiogenesis. A recent study shows that the specific vessel subtype, strongly positive for CD31 and Endomucin (CD31 hiEmcn hi), couples angiogenesis and osteogenesis. We found that preosteoclasts secrete platelet derived growth factor-BB (PDGF-BB), inducing CD31 hiEmcn hi vessels during bone modeling and remodeling. Mice with depletion of PDGF-BB in tartrate-resistant acid phosphatase positive (TRAP +) cell lineage ( Pdgfb –/–) show significantly lower trabecular and cortical bone mass, serum and bone marrow PDGF-BB concentrations, and CD31 hiEmcn hi vessels compared to wild-type mice. In the ovariectomized (OVX) osteoporotic mouse model, concentrations of serum and bone marrow PDGF-BB and CD31 hiEmcn hi vessels are significantly decreased. Inhibition of cathepsin K (CTSK) increases preosteoclast numbers, resulting in higher levels of PDGF-BB to stimulate CD31 hiEmcn hi vessels and bone formation in OVX mice. Thus, pharmacotherapies that increase PDGF-BB secretion from preosteoclasts offer a novel therapeutic target for osteoporosis to promote angiogenesis for bone formation.