Abstract: Objective To investigate the effect of inhibition and activation of MAPK-ERK1/2 pathway on the expression of
osteogenic genes and proliferation of rat osteoblasts in vitro. Methods Primarily cultured rat osteoblasts, identified by cell
morphology studies and ALP staining, were exposed to 1% or 5% rat serum for 24 h or to the specific MAPK-ERK1/2 inhibitor
PD0325901. The downstream molecules of MAPK-ERK1/2 pathway including p-ERK1/2 and ERK1/2, osteogenic genes such as
Runx2 and Type I collagen, and proliferating cell nuclear antigen (PCNA) were detected by Western Blotting, and alkaline
phosphatase activities were analyzed quantitatively. Results Compared with 1% rat serum-treated cells, exposure of the cells
to a higher concentration (5%) of rat serum caused a significantly increased phosphorylation level of p-ERK1/2 (P<0.05) and
obviously enhanced expressions of the osteogenic genes (Runx2, type I collagen and ALP) and PCNA (P<0.05). Inhibition of
the MAPK-ERK1/2 pathway with PD0325901 resulted in suppressed expressions of the osteogenic genes and PCNA.
Conclusion The activation of MAPK-ERK1/2 pathway promotes the expression of osteogenic genes such as Runx2, type I
collagen and ALP and enhances the proliferative activity of the osteoblasts, while inhibition of this pathway suppresses the
expressions of these genes and the cell proliferation, suggesting that this pathway may potentially serve as a therapeutic target
for osteoporosis.