Acitretin negatively regulates osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells

Acitretin, a widely used second-generation retinoid, has diverse systemic effects, yet its influence on osteogenic processes remains unclear. This study investigated the effects of acitretin on in vitro osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells (BMD-MSCs). BMD-MSCs were isolated from femur and tibia of six male Wistar rats (200-250 g, 4-6 weeks). At Passage 3, cells exhibited spindle-shaped morphology, expressed mesenchymal markers (CD90, CD44, CD29, CD54, and CD106), and lacked hematopoietic marker CD45. Multipotency was confirmed by adipogenic, chondrogenic, and osteogenic differentiation assays. Cells were then exposed to acitretin (10, 100, and 1000 µg/L) or vehicle (dimethyl sulfoxide, DMSO), and osteogenic differentiation was assessed at day 14 by Alizarin Red-S staining and semiquantitative RT-PCR analysis of collagen I alpha 2, osteonectin, and osteopontin expression. High-dose acitretin (1000 µg/L) significantly inhibited osteogenic differentiation, independent of DMSO, while lower concentrations showed no marked effect. These findings demonstrate that acitretin suppresses osteogenic differentiation of BMD-MSCs under in vitro conditions, suggesting potential implications for bone metabolism in patients receiving retinoid therapy. Further studies should focus on elucidating the mechanism of this effect, determining the frequency of skeletal system-related side effects in patients using retinoids, and determining the conditions of use of acitretin in high-risk patients.