Methoxsalen and Bergapten Prevent Diabetes-Induced Osteoporosis by the Suppression of Osteoclastogenic Gene Expression in Mice

Ham, Ju Ri; Choi, Ra-Yeong; Lee, Hae-In; Lee, Mi-Kyung

doi:10.3390/ijms20061298

Cited by 20 publications

(15 citation statements)

References 46 publications

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“…Coumarins derived from fruits of Cnidium monnieri exhibited beneficial anti-osteoporotic activity by inhibiting osteoclast activation [25]. In addition, coumarin derivatives of bergapten and methoxsalen prevent diabetic osteoporosis by suppressing osteoclastogenic gene expression and bone resorption in diabetic bone tissues [40]. However, little is known about the effects of coumarin on diabetes-associated abnormal bone turnover mediated via activation and differentiation of osteoclasts and osteoblasts.…”

Section: Discussionmentioning

confidence: 99%

Coumarin Ameliorates Impaired Bone Turnover by Inhibiting the Formation of Advanced Glycation End Products in Diabetic Osteoblasts and Osteoclasts

et al. 2020

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Accumulating evidence demonstrates that the risk of osteoporotic fractures increases in patients with diabetes mellitus. Thus, diabetes-induced bone fragility has recently been recognized as a diabetic complication. As the fracture risk is independent of the reduction in bone mineral density, deterioration in bone quality may be the main cause of bone fragility. Coumarin exists naturally in many plants as phenylpropanoids and is present in tonka beans in significantly high concentrations. This study investigated whether coumarin ameliorated the impaired bone turnover and remodeling under diabetic condition. The in vitro study employed murine macrophage Raw 264.7 cells differentiated to multinucleated osteoclasts with receptor activator of nuclear factor-κΒ ligand (RANKL) in the presence of 33 mM glucose and 1–20 μM coumarin for five days. In addition, osteoblastic MC3T3-E1 cells were exposed to 33 mM glucose for up to 21 days in the presence of 1–20 μM coumarin. High glucose diminished tartrate-resistant acid phosphatase activity and bone resorption in RANKL-differentiated osteoclasts, accompanying a reduction of cathepsin K induction and actin ring formation. In contrast, coumarin reversed the defective osteoclastogenesis in diabetic osteoclasts. Furthermore, high glucose diminished alkaline phosphatase activity and collagen type 1 induction of osteoblasts, which was strongly enhanced by submicromolar levels of coumarin to diabetic cells. Furthermore, coumarin restored the induction of RANK and osteoprotegerin in osteoclasts and osteoblasts under glucotoxic condition, indicating a tight coupling of osteoclastogenesis and osteoblastogenesis. Coumarin ameliorated the impaired bone turnover and remodeling in diabetic osteoblasts and osteoclasts by suppressing the interaction between advanced glycation end product (AGE) and its receptor (RAGE). Therefore, coumarin may restore optimal bone turnover of osteoclasts and osteoblasts by disrupting the hyperglycemia-mediated AGE–RAGE interaction.

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Section: Discussionmentioning

confidence: 99%

Coumarin Ameliorates Impaired Bone Turnover by Inhibiting the Formation of Advanced Glycation End Products in Diabetic Osteoblasts and Osteoclasts

et al. 2020

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“…Children suffering from T1DM were found to have low levels of osteocalcin, which were negatively correlated with HbA1c levels [82,83]. Derivatives of furanocoumarins reversed the suppression of osteocalcin and diabetes mellitus-associated decreased trabecular thickness in diabetic mice, in addition to significantly suppressing osteoclast-related gene expression such as RANKL [84]. When comparing T1DM and T2DM, osteocalcin serum levels are decreased in individuals living with T1DM and significantly decreased in T2DM compared to healthy controls [82,85,86,87].…”

Section: Bone Turnovermentioning

confidence: 99%

Impact of Diabetes Mellitus on Bone Health

Murray

Coleman

2019

IJMS

161

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Long-term exposure to a diabetic environment leads to changes in bone metabolism and impaired bone micro-architecture through a variety of mechanisms on molecular and structural levels. These changes predispose the bone to an increased fracture risk and impaired osseus healing. In a clinical practice, adequate control of diabetes mellitus is essential for preventing detrimental effects on bone health. Alternative fracture risk assessment tools may be needed to accurately determine fracture risk in patients living with diabetes mellitus. Currently, there is no conclusive model explaining the mechanism of action of diabetes mellitus on bone health, particularly in view of progenitor cells. In this review, the best available literature on the impact of diabetes mellitus on bone health in vitro and in vivo is summarised with an emphasis on future translational research opportunities in this field.

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“…After cleaning the adherent soft bone tissues and storing the bones in 70% ethyl alcohol, the femurs and tibias were analyzed using a high-resolution Skyscan micro-CT system (Skyscan 1272; Bruker, Billerica, MA, USA) and software as described previously [18]. The samples were scanned using a voxel size of 20.6 µm at 70 kV and 142 µA.…”

Section: Micro-computed Tomography (Micro-ct) Assaymentioning

confidence: 99%

“…Moreover, MTS has anticancer effects, which increase the level of cytotoxicity in human hepatoma cells [15] and human osteosarcoma cells [16]. Previous studies showed that MTS has anti-osteoporosis effects in ovariectomized and diabetic mice [17,18], but the effects of MTS on alcoholic liver diseases have not been reported. Therefore, this study examined the efficacy and underlying mechanism of MTS on chronic alcohol-induced osteopenia and steatosis in rats.…”

Section: Introductionmentioning

confidence: 99%

Protective Effects of Methoxsalen Supplementation on Chronic Alcohol-induced Osteopenia and Steatosis in Rats

Ham

hi³

et al. 2020

Molecules

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Osteopenia or osteoporosis occurs frequently in alcoholics and patients with alcoholic fatty liver disease. Methoxsalen (MTS), 8-methoxypsoralen, improved osteoporosis in ovariectomized and diabetic mouse models; however, its effects on alcohol-induced osteopenia and steatosis have not been reported. This study examined the effects of MTS on alcohol-induced bone loss and steatosis. Rats in the alcohol groups were fed a Liber-DeCarli liquid diet containing 36% of its calories as alcohol. MTS was at 0.005% in their diet, while alendronate (positive control; 500 μg/kg BW/day) was administered orally for eight weeks. The pair-fed group received the same volume of isocaloric liquid diet containing dextrin-maltose instead of alcohol as the alcohol control group consumed the previous day. In the alcohol-fed rats, the MTS and alendronate increased the bone volume density, bone surface density and trabecular number, while the bone specific surface, trabecular separation and structure model index were decreased in the tibia. MTS down-regulated tibial tartrate-resistant acid phosphatase 5 (TRAP) expression compared to the alcohol control group. MTS or alendronate prevented chronic alcohol-induced hepatic lipid accumulation and the triglyceride level in the alcohol-fed rats by decreasing the lipogenic enzyme activities and increasing the fatty acid oxidation enzyme activities. MTS reduced significantly the serum levels of alcohol, TRAP and tumor necrosis factor-α compared to the alcohol control group. Overall, these results suggest that MTS is likely to be an alternative agent for alcoholic osteopenia and hepatosteatosis.

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Methoxsalen and Bergapten Prevent Diabetes-Induced Osteoporosis by the Suppression of Osteoclastogenic Gene Expression in Mice

Cited by 20 publications

References 46 publications

Coumarin Ameliorates Impaired Bone Turnover by Inhibiting the Formation of Advanced Glycation End Products in Diabetic Osteoblasts and Osteoclasts

Coumarin Ameliorates Impaired Bone Turnover by Inhibiting the Formation of Advanced Glycation End Products in Diabetic Osteoblasts and Osteoclasts

Impact of Diabetes Mellitus on Bone Health

Protective Effects of Methoxsalen Supplementation on Chronic Alcohol-induced Osteopenia and Steatosis in Rats

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