Pleiotropic effects of the steroid hormone 1,25-dihydroxyvitamin D3 on the recruitment of mesenchymal lineage progenitors in fetal rat calvaria cell populations.
The steroid hormone 1,25-dihydroxyvitamin D3 (1,25(OH)(2)D(3)) inhibits osteogenesis while stimulating adipogenesis in vitro. We hypothesized that 1,25(OH)(2)D(3) 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)(2)D(3) 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)(2)D(3)-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)(2)D(3) 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)(2)D(3) 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 beta3 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)(2)D(3) treatment. The current studies demonstrate the global and developmental stage-specific effects of 1,25(OH)(2)D(3) on mesenchymal lineage progenitors, and suggest that the effects of 1,25(OH)(2)D(3) 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.
Zhang
Shulin
S
Department of Molecular and Medical Genetics, University of Toronto, Ontario, Canada M5S 1A8.
Chan
Melinda
M
Aubin
Jane E
JE
D000273:Adipose Tissue / Q000187:drug effects / Q000502:physiology; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002117:Calcitriol / Q000378:metabolism* / Q000494:pharmacology; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology; D051381:Rats; D012886:Skull / Q000166:cytology* / Q000502:physiology; D014815:Vitamins / Q000378:metabolism* / Q000494:pharmacology
D015415:Biomarkers; D014815:Vitamins; D002117:Calcitriol