Abstract
Tissue-engineered bone is a promising approach for repairing defects in the jawbone caused by tumors, infections, trauma, and congenital malformations, with BMP-2 playing a key role. Clinically, to achieve favorable therapeutic outcomes, the doses of BMP-2 used far exceed the physiological levels found in natural bone, leading to various side effects.To investigate the effectiveness and molecular mechanisms of the synergistic osteogenic action of dexamethasone (DEX) and BMP-2, and to explore effective methods to reduce the dosage of BMP-2 used. The effects of low concentration DEX (10− 8 M) and/or BMP-2 (100 ng/mL) on the morphology and activity of MC3T3-E1 cells were examined in various combinations. The efficacy of their combined use was verified through the detection of alkaline phosphatase, alizarin red staining, and the expression of osteogenesis-related genes. The molecular mechanism of their synergistic action was explored by detecting the expression of proteins in the Smad and p38 signaling pathways. The combined use of low concentration DEX and BMP-2 had no significant impact on the morphology and activity of MC3T3-E1 cells. Compared to the use of DEX or BMP-2 alone, their combined use enhanced the expression of alkaline phosphatase, increased calcium deposition, and significantly elevated the expression of osteogenesis-related genes such as ALP, RUNX2, OCN, and Col-1. Western blot analysis showed that the combined use of DEX and BMP-2 significantly increased the expression of Smad1/3/5, while p38 expression did not show a significant increase. The combined use of low concentration DEX and BMP-2 has a synergistic effect on osteogenic differentiation in MC3T3-E1 cells, acting through the BMPs-Smads signaling pathway rather than the p38-MAPK pathway. The results of this study are expected to reduce the dosage and dosage-related side effects of BMP-2 in jawbone repair, offering new strategies for the use of dosage and mode of growth factors in tissue-engineered bone.