Anabolic Effects of Vitamin D on Bone Remodeling : Correlation between Angiegenesis and Osteogenesis

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Human osteoblast-like cells (HOB) produces constitutionally vascular endothelial growth factor (VEGF) mRNA, and its steady state expression level is increased by active vitamin D (1, 25-(OH)2D3), (Wang DS, et al. J Bone Miner Res 11 : 472-479, 1996). It is well known that bone formation develops around blood vessels. 1, 25-(OH)2D3), which is most widely used for patients with osteoporosis, is capable of increasing (or at least maintaining) bone mineral density particularly in patients with senile osteoporosis.We therefore investigated weather 1, 25-(OH)2D3 is capable of stimulating proliferation and differentiation of HOB, when cocultured with human umbilical vein endothelial cells (HUVEC). 1, 25-(OH)2D3 did not stimulate proliferation of HOB alone, however, when HOB were cocultured with HUBEC, 1, 25-(OH)2D3 stimulated proliferation and differentiation of HOB.This anabolic effects were mediated by VEGF produced by HOB and insulin-like growth factor type I (IGF-1) and endothelin-1 produced by HUVEC.RT-PCR revealed that VEGF produced by HOB stimulated expression of VEGF receptors type I (FLT) and type II (KDR) in HUVEC (Wang DS, et al. Endocrinology 138 : 2953-2962, 1997).Furthermore, we have demonstrated that human growth hormone (hGH) elicits anabolic effects on HOB, by stimulating production of osteocalcin. HGH may stimulate bone remodeling by stimulating production of interleukin-6 (Wang DS, et al. Endocrine J.46 : 125-132, 1999). Weather hGH stimulates VEGF and IGF-1 in HOB and elicits anabolic effects on HOB is under the present investigation.