Biochemical Effects of Retinoid Derivatives on Mesenchymal Stem Cells In Vitro

The studies we performed targeted the effects of all-trans retinol (vitamin A) and some retinoid derivatives (including tretinoin or all-trans retinoic acid, retinyl propionate, 9-cis retinoic acid, 13-cis retinoic acid), as well as of tazarotenic acid on apoptosis of rat mesenchymal stem cells, cultured after isolation. Tazarotenic acid is considered to be relatively selective and a potent agonist for RAR beta and RAR gamma and less for RAR alpha. The same time, tazarotenic acid is not binding to RXRs (retinoid X receptors). The relevant analysis of our experimental results demonstrated that 13-cis retinoic acid was the most potent inducer of apoptosis of cultured mesenchymal stem cells of rat origin when compared to other retinoid derivatives, as follows: 13-cis retinoic acid > 9-cis retinoic acid > tazarotenic acid > all-trans retinoic acid > retinyl propionate > retinol (or vitamin A). Very interesting and unexpected were the apoptotic effects of 1 mu M tazarotenic acid for 24 hours in our experiments, very close to those induced by all-trans retinoic acid (tretinoin). The apoptosis induced by 13-cis retinoic acid, a principal activator of RAR beta and RAR gamma, and that induced by 9-cis retinoic acid, a major activator of RXRs, suggests different pathways activated by these retinoid derivatives.