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Department of Molecular and Medical Genetics, University of Toronto, Medical Sciences Building, 1 King’s College Circle, Toronto, Ontario, Canada M5S 1A8

(Requests for offprints should be addressed to J E Aubin; Email: jane.aubin{at}utoronto.ca)

(S Zhang is now at Division of Genetic Services, Department of Pathology and Molecular Medicine, Kingston General Hospital, Queen’s University, Kingston, ON, Canada K7 L 2 V7)

The steroid hormone 1,25-dihydroxyvitamin D3 (1,25(OH)₂D₃) inhibits osteogenesis while stimulating adipogenesis in vitro. We hypothesized that 1,25(OH)₂D₃ redirects the fate of osteoblast/adipocyte bipotential progenitors and other potential progenitors towards adipogenesis, a process possibly underlying the pathogenesis of osteopenic diseases such as osteoporosis. We therefore tested the global effects of 1,25(OH)₂D₃ on the recruitment of mesenchymal progenitors including osteogenic, chondrogenic, adipogenic and myogenic lineages (colony forming cell (CFC)-osteoblast (CFC-O), CFC-chondrocyte (CFC-C), CFC-adipocyte (CFC-A), and CFC-myoblast (CFC-M) respectively) in rat calvaria (RC) cell populations using gene expression profiling of single cell-derived colonies. Based on expression of lineage specific transcripts, 86% of single cell-derived colonies in untreated cultures simultaneously co-expressed transcripts of two, three, or four of the mesenchymal lineages tested. The distribution of mesenchymal progenitors in 1,25(OH)₂D₃-treated cultures was significantly changed compared with the control group, i.e. CFC-O were reduced (from 6 to 0%) and CFC-O/A bipotential (0 to 8.2%), CFC-C (4 to 10.2%) and CFC-Fibroblast (CFC-F) (4 to 16%) were increased. 1,25(OH)₂D₃ did not affect the frequency of tri- or tetra-lineage colonies. Single lineage CFC-A colonies were not detected in either the control or 1,25(OH)₂D₃ treatment group under the conditions tested.Since the parietal bones used for cell isolation derive from neuroectoderm, we also analyzed for expression of the neural markers nestin and ß3 tubulin in these colonies. Surprisingly, 90% (45 of 50) of the colonies in the control group expressed neural markers, a frequency not changed by 1,25(OH)₂D₃ treatment. The current studies demonstrate the global and developmental stage-specific effects of 1,25(OH)₂D₃ on mesenchymal lineage progenitors, and suggest that the effects of 1,25(OH)₂D₃ on osteogenesis and adipogenesis in RC populations are mediated, at least in part, by increased recruitment of CFC-O/A, but not CFC-A type precursors.

This article has been cited by other articles:

				J. E. Aubin Close Encounters of the Bone-Blood Kind IBMS BoneKEy, January 1, 2008; 5(1): 25 - 29. [Full Text] [PDF]

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