Vitamin K and D association stimulates in vitro osteoblast differentiation of fracture site derived human mesenchymal stem cells.

There is growing interest in osteoinductive agents for fracture healing especially in patients with non-union or delayed-union fractures. The aim of the present study is the assessment of the association of Vitamins D3 and K1 on proliferation and differentiation of human mesenchymal stem cells (hMSCs) derived from fracture sites in view of a possible clinical use. The synergic effect of Vitamin D3 and Vitamin K2 in preventing osteoporosis has been documented in clinical practice; however no reports investigating this association for fracture healing are present. Our data show 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 vitamin administration underline the differentiation of these cells into osteoblastic phenotype. Our results indicate for the first time that vitamin D3 and K1 association is able to modulate in vitro the differentiation towards osteoblastic phenotype of hMSCs derived from fracture sites, thus offering clinicians a promising and low-cost strategy for reparative osteogenesis.