Signal transducer and activator of transcription 3 positively regulates osteoblastic differentiation in MC3T3-E1 cells.

Abstract

Signal transducer and activator of transcription 3 (STAT3) plays a pivotal role in osteoblastic differentiation. However, the exact role of STAT3 in osteogenic differentiation of the pre-osteoblastic cell line MC3T3-E1 is still controversial. In this study, we demonstrated that eradication of STAT3 signaling by the inhibitors cryptotanshinone (CPT, a STAT3-specific inhibitor) or STAT3 siRNA both suppressed osteogenic differentiation of MC3T3-E1 cells, with a decrease in alkaline phosphatase (ALP) activity, protein expressions of the osteogenic differentiation markers Collagen I (ColI), ALP, and osteocalcin (OCN), and reduced matrix mineralization capacity at the terminal stage of osteogenic differentiation. However, the inhibition of STAT3 by CPT did not affect MC3T3-E1 cell proliferation. To further clarify the effect of STAT3 on osteogenic differentiation of MC3T3-E1 cells, we forced STAT3 expression and found that this ameliorated osteogenic differentiation. Thus, our results confirmed that STAT3 is a likely positive regulator of osteogenic differentiation in MC3T3-E1 cells. These findings may provide a basis for the development of more efficient and controllable protocols for osteoblastic differentiation and facilitate their use in regenerative medicine. In addition, our results provide novel insights into the effect of the STAT3 antagonist CPT on modulation of osteogenesis.