1,25-Dihydroxyvitamin D3 stimulates bone neovascularization by enhancing the interactions of osteoblasts-like cells and endothelial cells.

The current work investigated whether 1,25-dihydroxyvitamin D(3)(1,25-(OH)(2)D(3)) can promote the neovascularization of tissue-engineered bone. Human osteoblast-like cells (HOB) and endothelial cells (EC) were isolated and cultured. HOB and EC were inoculated at the ratio of 2:1 onto the coral-derived hydroxyapatite (CHA) scaffolds coated with and without 1,25-(OH)(2)D(3). Tissue-engineered bones were cultured for 3 days before implantation into the backs of nude mice. Four and 8 weeks after the operation, the retrieved scaffolds and cells were examined histologically and by scanning electron microscope, and the vascular area was measured. The immature bone grew into the pores of CHA scaffolds in both groups. At each time interval, there was a conspicuous neovascularization in the 1,25-(OH)(2)D(3) treatment group, with a larger amount of new capillaries accompanying immature bone. In the 1,25-(OH)(2)D(3) group, scanning electron microscopy revealed luminal sprouting from the larger vessels. Maturation of the new bone was paralleled by the occurrence of the new capillaries. The vascular areas were 28.74% +/- 7.81% and 19.52% +/- 4.57% at 4-week intervals (p < 0.05) and 24.66% +/- 7.38% and 17.84% +/- 5.22% at 8-week intervals (p < 0.05) in test and control groups, respectively. These results imply that 1,25-dihydroxyvitamin D(3) may be useful as a cytokine for tissue engineering bone for neovascularization.

[1]  Jennifer H. Elisseeff,et al.  Engineering Structurally Organized Cartilage and Bone Tissues , 2004, Annals of Biomedical Engineering.

[2]  D. P. O'connor,et al.  The incidence of fractures and dislocations referred for orthopaedic services in a capitated population. , 2004, The Journal of bone and joint surgery. American volume.

[3]  H. Pols,et al.  Vitamin D control of osteoblast function and bone extracellular matrix mineralization. , 2001, Critical reviews in eukaryotic gene expression.

[4]  U. Joos,et al.  Biological and biophysical principles in extracorporal bone tissue engineering. Part II. , 2004, International journal of oral and maxillofacial surgery.

[5]  M. Shibuya,et al.  Increase of vascular endothelial growth factor mRNA expression by 1,25‐dihydroxyvitamin D3 in human osteoblast‐like cells , 1996, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[6]  Linda G Griffith,et al.  Engineering principles of clinical cell-based tissue engineering. , 2004, The Journal of bone and joint surgery. American volume.

[7]  A. Meunier,et al.  Tissue-engineered bone regeneration , 2000, Nature Biotechnology.

[8]  J. Lieberman,et al.  Prefabrication of Bone by Use of a Vascularized Periosteal Flap and Bone Morphogenetic Protein , 2002, Plastic and reconstructive surgery.

[9]  Anthony Atala,et al.  Systems for therapeutic angiogenesis in tissue engineering , 2000, World Journal of Urology.

[10]  L. Haldosen,et al.  Effects of 1α, 25-dihydroxyvitamin D3 and growth hormone on apoptosis and proliferation in UMR 106 osteoblast-like cells , 2004 .

[11]  E. Jaffe,et al.  Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria. , 1973, The Journal of clinical investigation.

[12]  Rui L Reis,et al.  Bone tissue engineering: state of the art and future trends. , 2004, Macromolecular bioscience.

[13]  W. Lineaweaver,et al.  Vascular endothelial growth factor (VEGF) expression and the effect of exogenous VEGF on survival of a random flap in the rat. , 2003, British journal of plastic surgery.

[14]  Kanji Sato,et al.  Anabolic effects of 1,25-dihydroxyvitamin D3 on osteoblasts are enhanced by vascular endothelial growth factor produced by osteoblasts and by growth factors produced by endothelial cells. , 1997, Endocrinology.

[15]  L. Haldosen,et al.  1α,25-Dihydroxyvitamin D3 Inhibits GH-induced Expression of SOCS-3 and CIS and Prolongs Growth Hormone Signaling via the Janus Kinase (JAK2)/Signal Transducers and Activators of Transcription (STAT5) System in Osteoblast-like Cells* , 2002, The Journal of Biological Chemistry.

[16]  R. Kumar,et al.  Modulation of growth factor/cytokine synthesis and signaling by 1alpha,25-dihydroxyvitamin D(3): implications in cell growth and differentiation. , 2002, Endocrine reviews.

[17]  H. Redmond,et al.  Vascular endothelial growth factor stimulates bone repair by promoting angiogenesis and bone turnover , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[18]  A. Scutt,et al.  Short-term treatment of rats with high dose 1,25-dihydroxyvitamin D3 stimulates bone formation and increases the number of osteoblast precursor cells in bone marrow. , 1997, Endocrinology.

[19]  W. Morrison,et al.  Prefabricated Engineered Skin Flap Using an Arteriovenous Vascular Bundle as a Vascular Carrier in Rabbits , 2006, Plastic and reconstructive surgery.

[20]  M. Fukuda,et al.  Expression of various growth factors for cell proliferation and cytodifferentiation during fracture repair of bone. , 2000, European journal of histochemistry : EJH.

[21]  Safdar N. Khan,et al.  The Biology of Bone Grafting , 2005, The Journal of the American Academy of Orthopaedic Surgeons.

[22]  S. Papapoulos,et al.  Bone Morphogenetic Proteins Stimulate Angiogenesis through Osteoblast-Derived Vascular Endothelial Growth Factor A. , 2002, Endocrinology.

[23]  G. Finkenzeller,et al.  1,25-Dihydroxyvitamin D3 induces the expression of vascular endothelial growth factor in osteoblastic cells. , 1997, Endocrine research.

[24]  Y. Azuma,et al.  Serum 1α,25-Dihydroxyvitamin D3 Accumulates into the Fracture Callus during Rat Femoral Fracture Healing. , 1998, Endocrinology.