Gemigliptin attenuates reducing sugar-induced oxidative damage in MC3T3-E1 osteoblasts and improves osteoblastic differentiation

Abstract

Objective: Dipeptidyl peptidase-4 (DPP-4) inhibitors have been shown to reduce the rate of bone fractures. A newly developed antidiabetic drug, gemigliptin, may improve bone quality. We investigated the effects of gemigliptin on 2-deoxy-D-ribose (dRib)-induced oxidative damage and cellular dysfunction in the MC3T3-E1 osteoblastic cell line. Methods: Osteoblasts were treated with dRib, a strong reducing sugar, in the presence or absence of gemigliptin. Cell viability was evaluated using the CCK-8 assay. Apoptosis and reactive oxygen species (ROS) production were subsequently examined. The effects of gemigliptin on the expression of genes related to osteoblastic differentiation were determined via RT-PCR. Results: We observed that dRib reduced cell survival and markedly increased apoptosis and intracellular levels of ROS. However, pre-treatment with gemigliptin partially attenuated these dRib-induced effects. Additionally, treatment with gemigliptin increased alkaline phosphatase (ALP) activity and collagen production. Gemigliptin increased the expression of the bone-related markers ALP, collagen, osteocalcin, OPN, BMP2 and BMP7. The expression level of PI3K was increased after gemigliptin treatment under dRib condition. Conclusion: Taken together, these results suggest that gemigliptin attenuates dRib-induced cellular damage in osteoblasts. Gemigliptin may improve oxidative conditions in bone. Increased ALP activity and increased expression of genes related to osteoblastic differentiation indicate that gemigliptin treatment can improve the quality of bone formation. Our results suggest that gemigliptin treatment is effective in diminishing oxidative stress and improving bone strength through PI3K/AKT/BMP axis.