Abstract
Objectives
Diabetes mellitus is a complex disease with harmful effects on the osteoblast and osteoclast activity. Type 2 diabetic patients have normal or high bone mineral density but associated with an increased risk of fractures. Coumarins (1-benzopyran-2-one) are chemical compounds in the benzopyrone class of organic compounds found in many plants. The purpose of this study was to identify that hyperglycemia resulted in impaired bone remodeling and to examine whether coumarins were capable of preventing diabetic osteoporosis.
Methods
The in vitro study employed osteoblastic MC3T3-E1 cells that were exposed to 33 mM glucose for 6 days in the presence of 20 μM coumarins of scopoletin, aesculetin and coumarin. Alkaline phosphatase (ALP) activity was quantitatively determined in osteoblastic MC3T3-E1 cells by using stable p-nitrophenyl phosphate. In addition, murine macrophage Raw 264.7 cells were differentiated with receptor activator of nuclear factor-κΒ ligand (RANKL) in 33 mM glucose and 20 μM coumarins for 5 days. Tartrate-resistant acid phosphatase (TRAP) activity was measured using an assay kit.
Results
High glucose attenuated the ALP activity of osteoblastic MC3T3-E1 cells, which was enhanced by treating scopoletin, aesculetin and coumarin to cells. In addition, 33 mM glucose diminished TRAP activity in RANKL-differentiated Raw 264.7 macrophages, indicating that bone remodeling was impaired in diabetic osteoclasts. In contrast, scopoletin and coumarin elevated osteoclastic differentiation and activation. Interestingly, coumarin was highly effective in balancing bone turnover of osteoblasts and osteoclasts.
Conclusions
These results demonstrate that glucose evoked abnormal bone remodeling leading to diabetic bone disorder. In addition, coumarins such as scopoletin and coumarin ameliorated bone remodeling impaired in diabetic osteoblasts and osteoclasts. These findings suggest the possibility that coumarins might be a potential agent for the treatment of diabetic osteoporosis.
Funding Sources
This work (Grants No. C0501612) was supported by project for Cooperative R&D between Industry, Academy, and Research Institute funded Korea Ministry of SMEs and Startups in 20.