The effect of metformin and P38 MAPK inhibitor on diabetic bone porosity in non-obese type 2 diabetic rats

Abstract
Hyperglycemia enhances bone resorption and impairment. Controlling blood glucose via metformin benefits bonecells. Hyperglycemia enhances basal phosphorylation of p38 mitogen-activated protein kinase (MAPK), whichaggravates bone resorption. Therefore, the aim of this study was to assess the osteoprotective effects of metformin andp38 MAPK inhibitor in non-obese T2DM rats. In this study, non-obese T2DM (Goto-kakizaki, GK) rats were dividedinto four groups, including DM group, metformin treatment, SB203580 treatment, and metformin combined withSB203580. Wistar rats were used as control group. Femur, tibia, and iliac rat bones were collected to determine boneporosity via synchrotron radiation microtomography. Primary osteoblasts were isolated from calvaria to investigatecell proliferation and osteoblast function, including alkaline phosphatase (ALP) expression and calcium deposition.The results showed that diabetes increase bone porosity. Treatment with metformin significantly reduced porosity intrabecular and cortical bone of the femur, tibia, and iliac, while SB203580 significantly reduced porosity in corticalbone. A combination group showed significantly reduced bone porosity only in trabecular bone of the femur. Isolatedosteoblasts showed lower growth rates. Treatment with metformin significantly increased cell proliferation, ALPexpression, and calcium deposition. In summary, metformin treatment improved bone quality by reducing boneporosity, increasing cell proliferation, and improving osteoblast characteristics.
Description
Keywords
Goto-kakizaki, hyperglycemia, metformin, osteoporosis, p38 MAPK, type 2 diabetes.
Citation
Adulyaritthikul Punyanuch, Sanit Jantira, Nokkaew Nuttikarn, Kongpol Kantapich, Mongkolpathumrat Podsawee, Lampang Sakarat na, Catleya Rojviriya, Kumphune Sarawut. The effect of metformin and P38 MAPK inhibitor on diabetic bone porosity in non-obese type 2 diabetic rats. Journal of Applied Pharmaceutical Science. 2019 Jul; 2019 Jul: 082-090