BoneKEy Reports | BoneKEy Watch
Role for VEGF in osteoporosis development?
DOI:10.1038/bonekey.2012.217
Osteoporosis patients have bone marrow stem cells that differentiate preferentially into adipocytes, not osteoblasts. In this study, Liu et al. examined the possibility that expression of vascular endothelial growth factor (VEGF) in osteoblastic precursors determines the path of differentiation.
When VEGF expressed by mice osteoblasts was targeted conditionally, the mice developed with more bone marrow fat and lower bone mass, both phenotypic hallmarks of osteoporosis. As hypothesized, VEGF expression was reduced in mesenchymal stem cells, which pushed differentiation in favor of adipocytes rather than osteoblasts.
VEGF receptor 1 and VEGF receptor 2 are required for differentiation into osteoblasts; in vitro assays comparing cells treated with a VEGF-specific RNA silencer revealed that the VEGFR2 protein was apparently being produced normally, but the VEGFR1 protein was virtually undetectable compared to cells treated with control small hairpin RNA. The authors suggest that VEGFR1 may therefore be responsible for the nuclear localization of VEGF.
Further assays showed that cells in which VEGF expression had been silenced showed reduced RUNX2 transcriptional activity and increased levels of the lipid-activated transcription factor PPARĪ³2.
Editor's comment: This study demonstrates that VEGF stimulates differentiation of osteoblasts from bone marrow stem cells by increasing levels of RUNX2 expression and by suppressing PPARĪ³2 expression, as well as through a reciprocal interaction with nuclear envelope protein lamin A/C.
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