链脲佐菌素诱导的糖尿病患者外周管腔分支减少,与全骨极限载荷和周缘弹性功的减少有关

IF 3.4 Q2 ENDOCRINOLOGY & METABOLISM JBMR Plus Pub Date : 2024-01-04 DOI:10.1093/jbmrpl/ziad017
Morgan W. Bolger, Tara Tekkey, David H. Kohn
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引用次数: 0

摘要

骨细胞是骨骼中最丰富的细胞类型,对机械感觉、骨形成和骨吸收的信号传递非常重要,骨细胞驻留在一个复杂的裂隙-颅骨网络(OLCN)中。在糖尿病条件下,骨细胞信号传导会减少,1 型和 2 型糖尿病都会导致骨转换减少、骨组成紊乱和骨折风险增加。我们假设,糖尿病导致的骨转换减少和骨组成改变与 OLCN 结构和连接性降低有关。本研究旨在阐明:1)OLCN的变化顺序与糖尿病引起的骨转换有关;2)OLCN的变化是否与组织成分和机械性能有关。给 12-14 周大的雄性 C57BL/6 小鼠连续注射 5 天 50 毫克/千克的链脲佐菌素以诱导高血糖,在基线(BL)或糖尿病 3 周(D3)、7 周(D7)后与年龄匹配(C3、C7)的对照组(每组 10-12 只)一起处死。用罗丹明浸润矿化的股骨切片,并用共聚焦显微镜成像,然后描述 OLCN 的形态和拓扑结构,并将其与骨组织形态计量学、局部和整体骨力学及成分相关联。与 C7 小鼠相比,D7 小鼠的外周分支数量较少。与 BL 相比,D3 和 D7 小鼠的管状交叉点(节点)总数较低(P < 0.05),并且观察到 D7 小鼠的骨形成率(BFR)低于 C7 小鼠。节点数只能解释 15%的骨形成率,但能解释 45%的 Ct.BV/TV 和 31%的极限负荷。分支数量分别解释了皮质周围和皮质内区域 30% 和 22% 的弹性功。总之,OLCN结构的减少以及OLCN测量与骨转换、力学和组成的关联突出了骨细胞和OLCN的相关性,以及治疗糖尿病骨骼脆性的潜在治疗目标。
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Peripheral canalicular branching is decreased in streptozotocin-induced diabetes and correlates with decreased whole-bone ultimate load and perilacunar elastic work
Osteocytes are the most abundant cell type in bone, important for mechanosensation, signaling for bone formation, resorption and osteocytes reside in a complex lacuno-canalicular network (OLCN). Osteocyte signaling is reduced under diabetic conditions, and both type 1 and type 2 diabetes lead to reduced bone turnover, perturbed bone composition and increased fracture risk. We hypothesized this reduced bone turnover and altered bone composition with diabetes is associated with reduced OLCN architecture and connectivity. This study aimed to elucidate: 1) the sequence of OLCN changes with diabetes related to bone turnover, and 2) whether changes to the OLCN are associated with tissue composition and mechanical properties. 12–14 week old male C57BL/6 mice were administered streptozotocin at 50 mg/kg for 5 consecutive days to induce hyperglycemia, sacrificed at baseline (BL), or after being diabetic for 3 (D3), 7 (D7) weeks with age-matched (C3, C7) controls (n = 10–12 per group). Mineralized femoral sections were infiltrated with rhodamine, imaged with confocal microscopy, then the OLCN morphology and topology were characterized and correlated against bone histomorphometry, local and whole bone mechanics and composition. D7 mice exhibited a lower number of peripheral branches relative to C7. The total number of canalicular intersections (nodes) was lower in D3 and D7 relative to BL (p < 0.05 for all) and a reduced bone formation rate (BFR) was observed at D7 vs. C7. The number of nodes explained only 15% of BFR, but 45% of Ct.BV/TV, and 31% of ultimate load. The number of branches explained 30% and 22% of the elastic work at the perilacunar and intracortical region, respectively. Collectively, the reduction in OLCN architecture, and association of OLCN measures with bone turnover, mechanics and composition highlights the relevance of the osteocyte and the OLCN, and a potential therapeutic target for treating diabetic skeletal fragility.
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来源期刊
JBMR Plus
JBMR Plus Medicine-Orthopedics and Sports Medicine
CiteScore
5.80
自引率
2.60%
发文量
103
审稿时长
8 weeks
期刊最新文献
Bone mineral density over ten years after primary parathyroidectomy in multiple endocrine neoplasia type 1. Evaluating the relationship between glycemic control and bone fragility within the UK Biobank: observational and one-sample Mendelian randomization analyses. Correction to: Prevalence and risk factors for atypical femoral fracture among Lebanese patients with hip and shaft fractures. In nondiabetic C57BL/6J mice, canagliflozin affects the skeleton in a sex- and age-dependent manner. Genotype-phenotype correlations in 294 pediatric patients with osteogenesis imperfecta.
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