Enhancement of osteoinduction by vitamin D metabolites in rachitic host rats

Isaac Atkin, David D. Dean, Ofelia E. Muniz, Agueda Agundez, Greg Castiglione, Galit Cohen, David S. Howell, Asher Ornoy

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Diaphyseal bone from normal Sprague‐Dawley rats was delipidated in chloroform‐methanol and demineralized in 0.6 N HCl at 4°C. The bones were then implanted for 7–28 days into rats made rachitic by a low‐phosphate, vitamin D‐deficient diet (VDP) for 3 weeks. Bones from VDP and normal rats were also implanted into normal hosts. When normal rats were used as the host environment, a consistent sequence of cartilage induction and bone formation was observed. Demineralized rachitic bone (RB) implanted into normal host rats resulted in cartilage and bone induction similar to that seen for normal bone (NB) implants. Transmission electron microscopy of RB in normal hosts revealed morphologically normal chondrocytes and cartilage matrix with normal mineralization. In contrast, implantation of NB in VDP hosts resulted in delayed chondrogenesis and lack of calcification. Furthermore, similar results were observed when RB was implanted into VDP hosts. Treatment of VDP hosts with either 1α‐hydroxyvitamin D3 or 24,25‐dihydroxyvitamin D3 did not accelerate the sequential appearance of precartilage or cartilage. However, 24,25‐(OH)2D3 administered alone or in combination with 1α‐OHD3 significantly increased the amount of calcified cartilage observed at 2 weeks postimplantation compared to implants from either untreated VDP hosts or those treated only with 1α‐OHD3. New bone formation was observed at 4 weeks postimplantation in all vitamin D‐treated groups as determined by von Kossa staining or direct electron microscope examination. There was no apparent difference in the quantitative or qualitative bone formed within the various vitamin D‐treated groups. Serum calcium and phosphorus levels were lower and alkaline phosphatase levels were higher in VDP hosts compared with normal animals or those treated with vitamin D metabolites. The results of this study show a reduction in the capacity of progenitor cells in VDP rat hosts to respond to osteoinductive factor(s). This impaired response appears to be corrected by vitamin D metabolites.

Original languageEnglish
Pages (from-to)863-875
Number of pages13
JournalJournal of Bone and Mineral Research
Issue number8
StatePublished - Aug 1992
Externally publishedYes


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