Enríquez-Pérez Iris A, Galindo-Ordoñez Karla E, Pantoja-Ortíz Christian E, Martínez-Martínez Arisaí, Acosta-González Rosa I, Muñoz-Islas Enriqueta, Jiménez-Andrade Juan M
Unidad Académica Multidisciplinaria Reynosa Aztlán, Universidad Autónoma de Tamaulipas, Reynosa, Tamaulipas, 88740, Mexico.
Unidad Académica Multidisciplinaria Reynosa Aztlán, Universidad Autónoma de Tamaulipas, Reynosa, Tamaulipas, 88740, Mexico.
Neurosci Lett. 2017 Aug 10;655:28-34. doi: 10.1016/j.neulet.2017.06.042. Epub 2017 Jun 23.
Type-1 diabetes mellitus (T1DM) results in loss of innervation in some tissues including epidermis and retina; however, the effect on bone innervation is unknown. Likewise, T1DM results in pathological bone loss and increased risk of fracture. Thus, we quantified the density of calcitonin gene-related peptide (CGRP) sensory and tyrosine hydroxylase (TH) sympathetic nerve fibers and determined the association between the innervation density and microarchitecture of trabecular bone at the mouse femoral neck. Ten weeks-old female mice received 5 daily administrations of streptozocin (i.p. 50mg/kg) or citrate (control group). Twenty weeks later, femurs were analyzed by microCT and processed for immunohistochemistry. Confocal microscopy analysis revealed that mice with T1DM had a significant loss of both CGRP and TH nerve fibers in the bone marrow at the femoral neck. Likewise, microCT analysis revealed a significant decrease in the trabecular bone mineral density (tBMD), bone volume/total volume ratio (BV/TB), trabecular thickness (Tb.Th), trabecular number (Tb.N) and trabecular separation (Tb.Sp) in mice with T1DM as compared to control mice. Analysis of correlation revealed a positive and significant association between density of CGRP or TH nerve fibers with tBMD, BV/TV, Tb.Th and Tb.Sp, but not with trabecular number (there was a positive association only for CGRP) and degree of anisotropy (DA). This study suggests an interaction between sensory and sympathetic nervous system and T1DM-induced bone loss. Identification of the factors involved in the loss of CGRP sensory and TH sympathetic fibers and how they regulate bone loss may result in new avenues to treat T1DM-related osteoporosis.
1型糖尿病（T1DM）会导致包括表皮和视网膜在内的一些组织的神经支配丧失；然而，其对骨神经支配的影响尚不清楚。同样，T1DM会导致病理性骨质流失和骨折风险增加。因此，我们量化了降钙素基因相关肽（CGRP）感觉神经纤维和酪氨酸羟化酶（TH）交感神经纤维的密度，并确定了神经支配密度与小鼠股骨颈小梁骨微结构之间的关联。10周龄雌性小鼠每天接受5次链脲佐菌素腹腔注射（50mg/kg）或柠檬酸盐注射（对照组）。20周后，对股骨进行显微CT分析并进行免疫组织化学处理。共聚焦显微镜分析显示，患有T1DM的小鼠股骨颈骨髓中CGRP和TH神经纤维均显著减少。同样，显微CT分析显示，与对照小鼠相比，患有T1DM的小鼠小梁骨矿物质密度（tBMD）、骨体积/总体积比（BV/TB）、小梁厚度（Tb.Th）、小梁数量（Tb.N）和小梁间距（Tb.Sp）均显著降低。相关性分析显示，CGRP或TH神经纤维密度与tBMD、BV/TV、Tb.Th和Tb.Sp之间存在正相关且显著相关，但与小梁数量（仅CGRP存在正相关）和各向异性程度（DA）无关。本研究表明感觉神经系统和交感神经系统与T1DM诱导的骨质流失之间存在相互作用。确定参与CGRP感觉纤维和TH交感纤维丧失的因素以及它们如何调节骨质流失，可能会为治疗T1DM相关骨质疏松症带来新的途径。
