Abstract
This study evaluated whether bergapten and methoxsalen could prevent diabetes-induced osteoporosis and its underlying mechanism. For 10 weeks, bergapten or methoxsalen (0.02%, w/w) was applied to diabetic mice that were provided with a high-fat diet and streptozotocin. Bone mineral density (BMD) and microarchitecture quality were significantly reduced in the diabetic control group; however, both bergapten and methoxsalen reversed serum osteocalcin, bone-alkaline phosphatase and femur BMD. These coumarin derivatives significantly increased bone volume density and trabecular number, whereas they decreased the structure model index of femur tissue in diabetic mice. Conversely, tartrate-resistant acid phosphatase 5 (TRAP) staining revealed that these derivatives reduced osteoclast numbers and formation in diabetic bone tissue. Additionally, both bergapten and methoxsalen tended to downregulate the expression of osteoclast-related genes such as receptor activator of nuclear factor kappa-B ligand (RANKL), nuclear of activated T-cells, cytoplasmic 1 (NFATc1) and TRAP in diabetic femurs, with NFATc1 and TRAP expression showing significant reductions. Our data suggest that both bergapten and methoxsalen prevent diabetic osteoporosis by suppressing bone resorption.
Highlights
The prevalence of diabetes and osteoporosis are increasing worldwide, and these conditions have led to high morbidity and mortality among the elderly [1]
Serum insulin and adiponectin levels in DM decreased compared with the non-diabetic (NC) group, whereas blood glucose and glycosylated hemoglobin (HbA1c ) levels increased (Table 1)
Serum calcium (Ca) and inorganic phosphorus (IP) concentrations were significantly lower in DM than in the NC
Summary
The prevalence of diabetes and osteoporosis are increasing worldwide, and these conditions have led to high morbidity and mortality among the elderly [1]. Both type 1 (T1DM) and type 2 diabetes mellitus (T2DM) have been associated with decreased bone strength and increased risk of bone fractures [2]. Furanocoumarins, which occur in various herbal and citrus extracts, possess antibacterial, antioxidant, immunomodulator, apoptotic and anticancer activities [4]. After oral intake in both humans and animals, furanocoumarins can
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