INSTITUTIONAL DIGITAL REPOSITORY

Development of HFD-Fed/Low-Dose STZ-Treated female Sprague-Dawley rat model to investigate diabetic bone fragility at different organization levels

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dc.contributor.author Sihot, P.
dc.contributor.author Yadav, R. N.
dc.contributor.author Poleboina, S.
dc.contributor.author Mehandia, V.
dc.contributor.author Bhadada, S. K.
dc.contributor.author Tikoo, K.
dc.contributor.author Kumar, N.
dc.date.accessioned 2021-07-06T22:49:43Z
dc.date.available 2021-07-06T22:49:43Z
dc.date.issued 2021-07-07
dc.identifier.uri http://localhost:8080/xmlui/handle/123456789/2040
dc.description.abstract Type 2 diabetes (T2D) adversely affects the normal functioning, intrinsic material properties, and structural integrity of many tissues, and bone fragility is one of them. To simulate human T2D and to investigate diabetic bone fragility, many rodent diabetic models have been developed. Still, an outbred genetically normal nonobese diabetic rat model is not available that can better simulate the disease characteristics of nonobese T2D patients, who have a high prevalence in Asia. In this study, we used a combination treatment of high-fat diet (4 weeks, 58% kcal as fat) and low-dose streptozotocin (STZ; 35 mg/kg i.p. at the end of the fourth week) to develop T2D in female Sprague-Dawley (SD) rats. After 8 weeks of the establishment of the T2D model, the femoral bones were excised after euthanizing rats (animal age approximately 21 to 22 weeks; n = 10 with T2D, n = 10 without diabetes). The bone microstructure (μCT), mechanical, and material properties (three-point bending, cyclic reference point indentation, nanoindentation), mean mineral crystallite size (XRD), bone composition (mineral-to-matrix ratio, nonenzymatic cross-link ratio [NE-xLR], Fourier transform-infrared microspectroscopy), and total fluorescent advanced glycation end products were analyzed. We found that diabetic bone had reduced whole-bone strength and compromised structural properties (μCT). The NE-xLRs were elevated in the T2D group, and strongly and negatively correlated with postyield displacement, which suggests bone fragility was caused by a lack of glycation control. Along with that, the decreased mineral-to-matrix ratio and modulus, increased indentation distance increase, and wider mineral crystallite size in the T2D group were evidence that the diabetic bone composition and material properties had changed, and bone became weaker with a tendency to easily fracture. Altogether, this model simulates the natural history and metabolic characteristics of late-stage T2D (insulin resistance and as disease progress develops, hypoinsulinemia) for nonobese young (and/or adolescent) T2D patients (Asians) and provides potential evidence of diabetic bone fragility at various organization levels en_US
dc.language.iso en_US en_US
dc.subject BONE en_US
dc.subject COLLAGEN CROSS-LINKS en_US
dc.subject CRYSTALLITE SIZE en_US
dc.subject MATERIAL PROPERTY en_US
dc.subject NONOBESE RAT MODEL en_US
dc.subject TYPE 2 DIABETES en_US
dc.title Development of HFD-Fed/Low-Dose STZ-Treated female Sprague-Dawley rat model to investigate diabetic bone fragility at different organization levels en_US
dc.type Article en_US


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