Polyunsaturated fatty acids omega-3, but not the omega-6, stimulates the differentiation to osteoblasts of mesenchymal stem cell
Antonio Casado-Díaz1,2, Raquel Santiago-Mora1, Pilar Manso3 & José Manuel Quesada1,2
The compounds derived from the oxidative stress and lipid peroxidation stimulate the bone loss, in part because they enhance the adipogenesis and blunt the osteoblastogenesis from mesenchymal stem cell (MSC), increasing the marrow adiposity that accompanies the osteoporosis. The consumption of omega-3 seems to have a protective effect on bone. This effect has been associated with the production of 15-hydroxy-eicosapentaenoic acid and 17-hydroxy-docosahexaenoic acid, which do not trigger the adipogenic transcription factor PPAR-γ2, while the peroxidation of omega-6, produces 13-hydroxy octadecadienoic acid (HODE) and 15-hydroxytetraenoic acid (HETE), both PPARγ2 activators.
In this study MSCs were induced to differentiate to osteoblasts with 10−8 M dexamethasone, 10 mM β-glycerophosphate and 0.2 mM ascorbic acid, or to adipocytes with 5×10−7 M dexamethasone, 0.5 mM isobutylmethylxanthine and 50 μM indometacine ±40 or 20 μM of Araquidonic acid (AA) (omega-6), Docosahexaenoic acid (DHA) and Eicosapentaenoic acid (EPA) (omega-3).
In MSC cultures induced to osteoblasts the AA treatment decreased the expression of osteogenic markers and the ratio OPG/RANKL, while the DHA and EPA treatment increased it. Both treatments led the development of adipocytes. However, their number was always significantly higher in cultures treated with omega-6. In adipogenesis, the number of cells with vesicles of fat and adipogenesis markers increased significantly with the AA treatment. The AA treatment, also increase the production of 13-HODE and 15-HETE, as well as the expression of the gene lipoxygenase ALOX15B, both in the cultures induced to osteoblasts and induced to adipocytes.
This results indicate that the omega-3 stimulate the osteogenesis, and the omega-6 the adipogenesis of MSC, probably because the products of lipid peroxidation of the latter, produced by the lipoxygenase ALOX15B induces the expression of PPAR-γ2. Our data support preliminary observations, which have shown that a higher dietary omega-3/omega-6 fatty acids ratio is associated with beneficial effects on bone health.