FMS *Calciumfluor specifically increases mRNA levels and induces signaling via MAPK 42,44 and not FAK in differentiating rat osteoblasts

The homeopathic compound of resonance FMS*Calciumfluor (FMS*) reportedly promotes osteogenic differentiation of rat pre‐osteoblasts in vitro. Here, we show that the continuous exposure of differentiating rat osteogenic cells (ROB) to FMS* modulates the level of expression of mRNAs for 7 of the 8 osteogenic markers tested. Alkaline phosphatase (AP), osteocalcin (OC), metalloproteinases (MMP‐2 and −14), procollagenase C (BMP‐1), biglycan (BG) and integrin 1 are expressed at higher levels in FMS*‐treated osteoblasts than in control cultures. MMP‐2 and −14 mRNA are not down‐modulated at mineralization. Also, the pattern of expression induced by FMS* for some of these genes (BMP‐1, BG and integrin 1) is changed, but collagen type I (Coll I) mRNA levels are not affected by treatment with FMS*. This suggests that FMS* modulates mRNA levels and that this is not generalized, but gene(s) specific. We also report that exposure to FMS* rapidly and transiently induces activation of mitogen‐activated protein kinases (MAPKs) 42,44 in populations of early osteoblasts, but not in pre‐osteoblasts, with a cell differentiation stage‐dependent and pertussis toxin (PTX)‐sensitive response. Subsequent to FMS* MAPK signaling activation, an increase in AP and MMP‐14 mRNA is detected, which is also inhibited by PTX, suggesting that FMS* activation of MAPK signaling could be an early event required for the induction of these genes. Exposure to FMS* does not cause changes in the activity of p125 (FAK)‐mediated signaling.