Effects of vitamin D metabolites on axolotl limb regeneration

Abstract

Vitamin D is essential for normal metabolism of phosphorus and calcium, and differentiation of skeletal elements. 1,25 dihydroxyvitamin-D₃ , the biologically active metabolite, acts as an induction/proliferation switch in various cell types and promotes chondrogenesis of chick limb bud mesenchymal cells. The function of vitamin D is mediated through its nuclear receptor, the vitamin D receptor (VDR). The proliferative actions of 1,25(OH)₂ -D₃ on limb bud mesenchymal cells are similar to the ones produced by retinoids, such as all-trans retinoic acid (RA) or 9-cis retinoic acid (9-cis). The retinoids have been shown to be compounds of extreme importance in the field of limb development and regeneration. In order to examine possible roles of vitamin D metabolites on limb regeneration, the effects of 1,25(OH)₂ -D₃ , 24,25(OH)₂ -D₃ and KH1060 (a more potent metabolite) alone or in conjunction with all-trans RA or 9-cis RA on the regenerating axolotl limb. Vitamin D affects limb morphogenesis by generating abnormalities in skeletal elements. Synergism of vitamin D with retinoic acid in affecting pattern formation is suggested by the results.

Keywords: limb; regeneration; steroid receptors; urodeles; vitamin D.