Kaur Japneet, Brooks Hannah W, Froemming Mitchell N, Cusick Nicholas C, Funk Janet L, Farr Joshua N
Department of Physiology and Cell Biology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Clinical and Translational Science, University of Arizona, Tucson, AZ, 85721, USA.
Calcif Tissue Int. 2025 Jul 1;116(1):93. doi: 10.1007/s00223-025-01401-w.
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.
1型糖尿病（T1D）和2型糖尿病（T2D）与骨骼脆弱有关，会增加骨折风险。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。这些差异尚未完全了解，但可能源于不同的机制。此前，我们发现患有T2D的肥胖雄性C57BL/6小鼠（7个月大）表现出骨质不佳和骨细胞衰老加速，并伴有独特的衰老相关分泌表型（SASP）。我们推测，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中会积累。与之前的研究一致，我们研究了一个幼年发病（2个月大）的T1D模型，8周后，患有T1D的雄性C57BL/6小鼠的骨微结构恶化，皮质孔隙率增加，骨强度降低。出乎意料的是，T1D小鼠中的骨细胞、髓样细胞、T细胞和B细胞在关键衰老/SAPS标志物方面没有显著变化。因此，尽管T1D小鼠表现出骨质不佳的几个方面，与人类幼年发病的T1D一致，但在这个年轻阶段，衰老细胞尚未在骨骼中大量积累。未来的研究应包括雌性小鼠，并测试衰老是否需要T1D发病较晚、病程较长或血糖控制较差。
