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

H Xie, Z Cui, L Wang, Z Xia, Y Hu, L Xian, C Li, L Xie… - Nature medicine, 2014 - nature.com
H Xie, Z Cui, L Wang, Z Xia, Y Hu, L Xian, C Li, L Xie, J Crane, M Wan, G Zhen, Q Bian, B Yu…
Nature medicine, 2014nature.com
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 …
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 (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.
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