Examination of Skeletal and Senescence Phenotypes in Young Mice with Juvenile Onset Type 1 Diabetes.

IF 3.3 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM
Japneet Kaur, Hannah W Brooks, Mitchell N Froemming, Nicholas C Cusick, Janet L Funk, Joshua N Farr
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Abstract

Type 1 diabetes (T1D) and T2D are associated with skeletal fragility, contributing to increased fracture risk. Whereas decreased bone mineral density (BMD) is common in T1D, individuals with T2D tend to have normal or elevated BMD. These differences are incompletely understood but may stem from distinct mechanisms. Previously, we showed that obese male C57BL/6 mice (7-month-old) with T2D exhibit poor bone quality and accelerated osteocyte senescence with a unique senescence-associated secretory phenotype (SASP). We hypothesized that, similar to T2D, senescent osteocytes and additional senescent bone-resident cells (e.g., immune cells) accumulate in T1D. Consistent with previous studies, we studied a juvenile onset (2-month-old) T1D model, where following 8 weeks, male C57BL/6 mice with T1D displayed deteriorated bone microarchitecture, increased cortical porosity, and reduced bone strength. Unexpectedly, osteocytes, myeloid cells, T cells, and B cells in T1D mice showed no significant changes in key senescence/SAPS markers. Therefore, although T1D mice display several aspects of poor bone quality, consistent with juvenile-onset T1D in humans, senescent cells have yet to accumulate at substantial levels in bone at this young age. Future studies should include female mice and test whether senescence requires a later onset of T1D, a longer disease duration, or worse glycemic control.

幼年发病1型糖尿病小鼠骨骼和衰老表型的研究。
1型糖尿病(T1D)和T2D与骨骼脆弱相关,导致骨折风险增加。虽然骨密度(BMD)降低在T1D中很常见,但T2D患者的骨密度往往正常或升高。这些差异尚不完全清楚,但可能源于不同的机制。先前,我们发现患有T2D的肥胖雄性C57BL/6小鼠(7月龄)表现出骨质量差和骨细胞衰老加速,并具有独特的衰老相关分泌表型(SASP)。我们假设,与T2D类似,衰老的骨细胞和其他衰老的骨驻留细胞(如免疫细胞)在T1D中积累。与之前的研究一致,我们研究了幼年发病(2个月)的T1D模型,在8周后,患有T1D的雄性C57BL/6小鼠表现出骨微结构恶化,皮质孔隙度增加,骨强度降低。出乎意料的是,T1D小鼠的骨细胞、骨髓细胞、T细胞和B细胞在关键的衰老/SAPS标志物上没有明显变化。因此,尽管T1D小鼠在几个方面表现出较差的骨质量,与人类青少年发病的T1D一致,但衰老细胞尚未在如此年轻的年龄在骨骼中积累大量水平。未来的研究应该包括雌性小鼠,并测试衰老是否需要更晚的T1D发病时间、更长的疾病持续时间或更差的血糖控制。
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来源期刊
Calcified Tissue International
Calcified Tissue International 医学-内分泌学与代谢
CiteScore
8.00
自引率
2.40%
发文量
112
审稿时长
4-8 weeks
期刊介绍: Calcified Tissue International and Musculoskeletal Research publishes original research and reviews concerning the structure and function of bone, and other musculoskeletal tissues in living organisms and clinical studies of musculoskeletal disease. It includes studies of cell biology, molecular biology, intracellular signalling, and physiology, as well as research into the hormones, cytokines and other mediators that influence the musculoskeletal system. The journal also publishes clinical studies of relevance to bone disease, mineral metabolism, muscle function, and musculoskeletal interactions.
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