Induction and rescue of skeletal fragility in a high-fat diet mouse model of type 2 diabetes: An in vivo and in vitro approach.
Induction and rescue of skeletal fragility in a high-fat diet mouse model of type 2 diabetes: An in vivo and in vitro approach.
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DOI：
10.1016/j.bone.2021.116302
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发表时间：
2022-03
期刊：
影响因子：
4.1
通讯作者：
Vashishth D
中科院分区：
文献类型：
--
作者：
LLabre JE;Sroga GE;Tice MJL;Vashishth D
Poor bone quality is associated with Type 2 Diabetes (T2D), with patients having a higher risk of fracture despite normal to high bone mineral density (BMD). Diabetes contributes to modifications of the mineral and organic matrix of bone. Hyperglycemia has been linked to the formation of advanced glycation end-products (AGEs) which increase the risk for skeletal fragility fractures. To this end, we investigated diabetes-induced skeletal fragility using a high-fat diet (HFD) mouse model and evaluated the efficacy of phenacyl thiazolium chloride (PTC) for in vitro removal of glycation products to rescue bone toughness. Ten-week-old C57BL/6J male mice (n=6/group) were fed a HFD or low-fat diet (LFD) for 22 weeks. Mice given a HFD developed T2D and increased body mass compared to LFD-fed mice. MicroCT results showed that diabetic mice had altered microarchitecture and increased mineralization as determined by volumetric BMD and increased mineral crystal size as determined by X-ray Diffraction (XRD). Diabetic mice demonstrated loss of initiation and maximum toughness, which represent estimates of the stress intensity factor at a notch tip using yield force and ultimate force, respectively. Diabetic mice also showed higher accumulation of AGEs measured by biochemical assay (total fAGEs) and confocal Raman spectroscopy (Pentosidine (PEN), Carboxymethyl-lysine (CML)). Regression analyses confirmed the association between increased glycoxidation (CML, PEN) and loss of fracture toughness. Within the diabetic group, CML was the most significant predictor of initiation toughness while PEN predicted maximum toughness as determined by stepwise linear regression (i.e., stepAIC). Contralateral femora from HFD group were harvested and treated with PTC in vitro. PTC-treated samples showed total fAGEs decreased by 41.2%. PTC treatment partially restored bone toughness as, compared to T2D controls, maximum toughness increased by 35%. Collectively, our results demonstrate that matrix modifications in diet-induced T2D, particularly AGEs, induce bone fragility and their removal from bone matrix partially rescues T2D associated bone fragility.
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影响因子：
8.2
作者：
Cooper, ME;Thallas, V;Soulis, T
通讯作者：
Soulis, T
DOI：
10.1152/ajpendo.90617.2008
发表时间：
2008-12-01
影响因子：
5.1
作者：
Andrikopoulos, Sofianos;Blair, Amy R.;Proietto, Joseph
通讯作者：
Proietto, Joseph
影响因子：
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作者：
Carvalho, Marta S.;Silva, Joao C.;Vashishth, Deepak
通讯作者：
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影响因子：
4.2
作者：
Creecy A;Uppuganti S;Merkel AR;O'Neal D;Makowski AJ;Granke M;Voziyan P;Nyman JS
通讯作者：
Nyman JS
影响因子：
4.2
作者：
Gamsjaeger, Sonja;Robins, Simon P.;Paschalis, Eleftherios P.
通讯作者：
Paschalis, Eleftherios P.