PDGF-BB secreted by preosteoclasts induces CD31(hi)Emcn(hi) vessel subtype in coupling osteogenesis

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(hi)Emcn(hi)), couples angiogenesis and osteogenesis. We found that preosteoclasts secrete platelet derived growth factor-BB (PDGF-BB), inducing CD31(hi)Emcn(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(hi)Emcn(hi) vessels compared to wild-type mice. In the ovariectomized (OVX) osteoporotic mouse model, concentrations of serum and bone marrow PDGF-BB and CD31(hi)Emcn(hi) vessels are significantly decreased. Inhibition of cathepsin K (CTSK) increases preosteoclast numbers, resulting in higher levels of PDGF-BB to stimulate CD31(hi)Emcn(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.