*3.2.2.4 Effect of statins on cell differentiation and ECM composition*

Simvastatin modulates cell differentiation through the IL-6-dependent PTHrP/ Ras/MAPK pathway in human osteoblasts and MG-63 osteosarcoma cells, increasing the level of bone differentiation markers like alkaline phosphatase activity and/ or osteocalcin [72]. BMP-2-dependent osteoblast differentiation is stimulated by lipophilic statins, while the hydrophilic statin pravastatin does not [72], also modifying osteoblast differentiation markers collagen, alkaline phosphatase, and osteocalcin [73]. Statins also promote cell differentiation of Ewing's sarcoma [66].
