RESUMO
Human gingival fibroblasts (HGFs) are responsible for connective tissue repair and scarring, and are exposed to mechanical forces under physiological and pathological conditions. The exact mechanisms underlying gingival tissue reconstruction under mechanical forces remain unclear. The present study aimfed to investigate the effects of mechanical forces on the proliferation and extracellular matrix synthesis in HGFs by establishing a 3dimensional (3D) HGF culture model using poly(lactidecoglycolide) (PLGA) scaffolds. HGFs were cultured in 3D PLGA scaffolds and a mechanical force of 0, 5, 15, 25 or 35 g/cm2 was applied to HGFs for 24 h. A mechanical force of 25 g/cm2 induced the highest proliferation rate, and thus was selected for subsequent experiments. Cell viability was determined using the MTT assay at 0, 24, 48 and 72 h. The expression levels of type I collagen (COL1) and matrix metallopeptidase (MMP)1 were examined by reverse transcriptionquantitative polymerase chain reaction and ELISA, and transforming growth factor (TGF)ß expression was evaluated by ELISA. The application of mechanical force on HGFs cultured on the 3D PLGA scaffolds resulted in a significant increase in cell proliferation and COL1 expression, as well as a decrease in MMP1 expression. A TGFß1 inhibitor was also applied, which attenuated the effects of mechanical force on HGF proliferation, and COL1 and MMP1 expression, thus suggesting that TGFß signaling pathways may mediate the mechanical forceinduced alterations observed in HGFs. In conclusion, these findings helped to clarify the mechanisms underlying mechanical forceinduced HGF proliferation and ECM synthesis, which may promote the development of targeted therapeutics to treat various diseases, including gingival atrophy caused by orthodontic treatment.