PDGF-BB secreted by preosteoclasts induces angiogenesis during coupling with osteogenesis.
Nat Med
; 20(11): 1270-8, 2014 Nov.
Article
de En
| MEDLINE
| ID: mdl-25282358
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 (CD31(hi)Emcn(hi)), couples angiogenesis and osteogenesis. Here, we found that platelet-derived growth factor-BB (PDGF-BB) secreted by preosteoclasts induces CD31(hi)Emcn(hi) 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 CD31(hi)Emcn(hi) 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 CD31(hi)Emcn(hi) 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 CD31(hi)Emcn(hi) 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.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Ostéoclastes
/
Ostéogenèse
/
Néovascularisation physiologique
/
Protéines proto-oncogènes c-sis
Type d'étude:
Prognostic_studies
Langue:
En
Journal:
Nat Med
Sujet du journal:
BIOLOGIA MOLECULAR
/
MEDICINA
Année:
2014
Type de document:
Article
Pays d'affiliation:
Chine