IBMS BoneKEy | BoneKEy Watch
PDGF-BB—a key link between angiogenesis and osteogenesis
DOI:10.1038/bonekey.2015.26
Blood vessels that express high levels of CD31 and endomucin (CD31hiEmcnhi) have been discovered recently and appear to couple together osteogenesis and angiogenesis. In this study, Xie et al. looked in more detail at this coupling mechanism.
After showing that platelet-derived growth factor BB (PDGF-BB) is responsible for initiating formation of CD31hiEmcnhi vessels, the authors showed that PDGF-BB is produced by preosteoclasts during both bone modeling and bone remodeling.
Knock out mice bred with a specific deletion of PDGF-BB in cells expressing tartrate-resistant acid phosphatase (TRAP) had lower concentrations of PDGF-BB in their serum and bone marrow, fewer CD31hiEmcnhi blood vessels and significantly reduced cortical and trabecular bone mass.
A very similar phenotype was observed in ovariectomized mice that exhibited osteoporotic symptoms. When these mice were treated with PDGF-BB or with a cathepsin K inhibitor, the number of CD31hiEmcnhi blood vessels increased and the formation of new bone tissue was stimulated.
Editor’s comment: By demonstrating that preosteoclasts release vascular growth factors, this study shows that the role that osteoclasts play in bone formation extends way beyond the bone remodeling processes. Perhaps even more interestingly is the finding that cathepsin K inhibition increases bone vascularization, a process that could contribute to the cortical bone formation observed in some preclinical models in which new cathepsin K inhibitors have been tested as potential therapies osteoporosis.
This work is licensed under a
Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 United States License.