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 shows that the specific vessel subtype, strongly positive for CD31 and Endomucin (CD31hiEmcnhi), couples angiogenesis and osteogenesis. We found that preosteoclasts secrete platelet derived growth factor-BB (PDGF-BB), inducing CD31hiEmcnhi 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 CD31hiEmcnhi vessels compared to wild-type mice. In the ovariectomized (OVX) osteoporotic mouse model, concentrations of serum and bone marrow PDGF-BB and CD31hiEmcnhi vessels are significantly decreased. Inhibition of cathepsin K (CTSK) increases preosteoclast numbers, resulting in higher levels of PDGF-BB to stimulate CD31hiEmcnhi 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.

Graphene‐Based MicroRNA Transfection Blocks Preosteoclast Fusion to Increase Bone Formation and Vascularization

“…Since POCs are beneficial for bone formation, mineralization, and angiogenesis through coupling with osteoblasts and secreting platelet derived growth factor‐BB (PDGF‐BB) 8, 9. We then used BMMs and MSCs coculture system to test the effect of GO‐PEI‐miR‐7b treated osteoclast on osteogenesis ( Figure 4 a).…”

“…Their abundance is intimately associated with new bone formation. It has also been proved that PDGF‐BB secreted by POCs induces the formation of CD31 hi Emcn hi vessels in coupling bone formation 8. To find out if GO‐PEI‐miR‐7b could enhance angiogenesis in vivo, we performed immunofluorescent analysis on TRAP and PDGF‐BB of the distal femur ( Figure 6 a).…”

“…The reason is that bisphosphonate inhibits both preosteoclast (POC) and mature OC without selectivity 3, 7. However, according to recent discoveries, POCs barely resorb bone matrix, on the contrary, they are beneficial for angiogenesis through secreting platelet derived growth factor‐BB (PDGF‐BB) 8, 9, 10. This is why current long‐term antiresorptive therapy is not satisfying and even increases risk of atypical fractures 11.…”

Assessment of bone vascularization and its role in bone remodeling

“…Deferoxamin treatment, which stabilizes HIF-1a, was osteogenic and led to substantial expansion of type H endothelium and emergence of vesselassociated osteoprogenitors in aged animals. Xie et al 20 further showed that platelet-derived growth factor-BB, exogenous or released by preosteoclasts, induces type H vessel and stimulates bone formation in OVX mice. Altogether, these exciting data emphasize the high heterogeneity of bone vasculature and clearly identify the bone vessel as a therapeutic target in metabolic bone diseases.…”

The posterior HOXD locus: Its contribution to phenotype and malignancy of Ewing sarcoma

“…Interestingly, RUNX2 expression was not consistently affected after single knock down of each HOXD gene (data not shown) even after incubation in osteogenic differentiation media (see Supplementary Material, Figure S4C). But, posterior HOXD genes clearly promoted the expression of additional genes important for ossification or endochondral bone development in ES such as osteoblast-specific gene osteocalcin (bone gamma-carboxyglutamate (gla) protein, BGLAP), the pre-/osteoclast specific factor plateletderived growth factor beta polypeptide (PDGFB) [36] ( Figure 3C) or induction of osteolytic ES growth typical PTHLH [5] (Figure 3D), respectively.…”