Johns Hopkins University2014-12-03 3:27 PM

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

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 .


Full Article:

http://www.nature.com/nm/journal/v20/n11/full/nm.3668.html

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