scholarly journals Hydroxycoumarin Scopoletin Inhibits Bone Loss through Enhancing Induction of Bone Turnover Markers in a Mouse Model of Type 2 Diabetes

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 648
Author(s):  
Eun-Jung Lee ◽  
Woojin Na ◽  
Min-Kyung Kang ◽  
Yun-Ho Kim ◽  
Dong-Yeon Kim ◽  
...  

Diabetes induces bone deterioration, which leads to increased risk of fracture, osteopenia, and osteoporosis. Thus, diabetes-associated bone fragility has been recognized as a diabetic complication. However, the pathophysiological effects of hyperglycemia on bone turnover remain unclear. Literature evidence demonstrates that anti-diabetic medications increase the risk of fractures in individuals with type 2 diabetes. Scopoletin is a naturally occurring hydroxycoumarin potentially exhibiting anti-inflammatory and antioxidant activities and ameliorating insulin resistance as an anti-diabetic agent. However, little is known regarding the effects of scopoletin on the impairment of bone remodeling that is caused by diabetes. The aim of this study was to identify that scopoletin was capable of inhibiting the impairment of bone remodeling and turnover in a mouse model of type 2 diabetes. Submicromolar scopoletin accelerated the formation TRAP-positive multinucleated osteoclasts (40.0 vs. 105.1%) and actin ring structures impaired by 33 mM glucose. Further, 1–20 μM scopoletin enhanced bone resorption and the induction of matrix-degrading enzymes in diabetic osteoclasts. The oral administration of 10 mg/kg scopoletin elevated serum RANKL/OPG ratio and osteocalcin level reduced in db/db mice along with an increase in BMD by ~6–14%; however, it was not effective in lowering blood glucose and hemoglobin glycation. In addition, the supplementation of scopoletin elevated the formation of trabecular bones and collagen fibers in femoral epiphysis and metaphysis with a thicker epiphyseal plate and cortical bones. Furthermore, 1–20 μM scopoletin enhanced ALP activity (4.39 vs. 7.02 nmol p-nitrophenyl phosphate/min/mg protein) and deposits of mineralized bone nodules in cultured osteoblasts reduced by 33 mM glucose. The treatment of diabetic osteoblasts with scopoletin stimulated the cellular induction of BMP-2 and osteopontin and Runx2 transcription. Accordingly, the administration of scopoletin protected mice from type 2 diabetes-associated bone loss through boosting bone remodeling via the robust induction of bone turnover markers of both osteoclasts and osteoblasts. These findings suggest that scopoletin could be a potential osteoprotective agent for the treatment of diabetes-associated bone loss and fractures.

2008 ◽  
Vol 36 (6) ◽  
pp. 1392-1398 ◽  
Author(s):  
I Capoglu ◽  
A Ozkan ◽  
B Ozkan ◽  
Z Umudum

The aim of this prospective, longitudinal study was to investigate, over a period of 12 months, the effects of metabolic control on bone turnover markers in patients with type 2 diabetes mellitus. The study included 17 male and 18 female patients with type 2 diabetes, aged 37 − 66 years. Mean follow-up period was 12 ± 1.2 months. Mean glycosylated haemoglobin (HbA1C) levels were 10.6% ± 1.6% at the start of the study and decreased to 7.7% ± 1.0% by the end of the study. Levels of the bone resorption markers, urinary deoxypyridinoline and N-telopeptide, were 28.6 ± 11.6 nmol/mmol creatinine and 93.6 ± 13.7 nmol bone collagen equivalents [BCE]/mmol creatinine, respectively, at the start of the study, and decreased significantly to 17.9 ± 7.1 nmol/mmol creatinine and 67.8 ± 12.8 nmol BCE/mmol creatinine, respectively, by the end of the study. Bone formation parameters also significantly decreased in parallel with HbA1c levels over the study period. It is concluded that effective management of metabolic disorder in patients with type 2 diabetes plays an important contribution to bone turnover improvement.


2021 ◽  
Vol 10 (4) ◽  
pp. 378-386
Author(s):  
Haojie Zhang ◽  
Yuke Cui ◽  
Ruihua Dong ◽  
Wen Zhang ◽  
Shihan Chen ◽  
...  

Background Bone is thought to be the reservoir of the human lead burden, and vitamin D is associated with bone turnover. We aimed to explore whether exposure to lower 25-hydroxy vitamin D (25(OH)D) levels was associated with higher blood lead levels (BLLs) by increasing the bone turnover rate in individuals with type 2 diabetes. Methods A total of 4103 type 2 diabetic men and postmenopausal women in Shanghai, China, were enrolled in 2018. Their 25(OH)D, β-C-terminal telopeptide (β-CTX), N-MID osteocalcin and procollagen type 1 N-peptide (P1NP) levels were detected. Their BLLs were determined by atomic absorption spectrometry. Mediation analyses were performed to identify the possible role that bone turnover played in the underlying mechanisms. Results In both the men and postmenopausal women, all three bone turnover markers were inversely associated with 25(OH)D and positively associated with the BLL (all P < 0.01) after adjusting for age, current smoking habits, metabolic parameters, duration of diabetes, vitamin D intake, and use of anti-osteoporosis medication. In the mediation analyses, none of the direct associations between 25(OH)D and BLL was significant for the three bone turnover markers, but all three bone turnover markers were found to be significant mediators of the indirect associations between 25(OH)D and BLL. Conclusion The association between vitamin D and BLL was fully mediated by bone turnover markers in type 2 diabetic patients (mediation effect). This finding suggested that vitamin D may protect against blood lead exposure from the bone reservoir by decreasing bone turnover in individuals with type 2 diabetes.


Author(s):  
SwetaVilas Kulkarni ◽  
Suruthi Meenatchi ◽  
R Reeta ◽  
Ramasamy Ramesh ◽  
AR Srinivasan ◽  
...  

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