There is a growing interest on osteoinductive agents for fracture healing especially in patients with non-union or delayed-union fractures. Aim of the present study was the assessment of the association of Vitamins D3 and K1 on proliferation and differentiation of human mesenchymal stem cells (hMSCs) derived from facture site in view of a possible clinical use. The synergic effect Vitamin D3 and Vitamin K2 in preventing osteoporosis has been documented in clinical practice, however no report investigating this association for fracture healing are present. Our data showed a different outcome on cell proliferation linked to the different timing of drug administration as well as a synergic effect of the two vitamins on cell differentiation. The high level of osteocalcin and carboxylated osteocalcin detected in hMSCs treated with the association of the two vitamins in comparison with controls and with single vitamins administration underline the differentiation of these cells into osteoblastic phenotype. Our result indicate for the first time that the vitamin D3and K1 association is able to modulate in vitro the differentiation towards osteoblastic phenotype of hMSCs derived from fracture sites, thus offering to clinicians a promising and low-cost strategy for reparative osteogenesis.
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