骨形成和骨吸收中骨细胞的作用探究(2)
来源：学术堂 作者：原来是喵
发布于：2016-11-14 共8811字
3骨细胞的内分泌功能
考虑到骨细胞深埋于矿化的骨基质中，似乎远离其他细胞和器官，把骨细胞归类于内分泌细胞似乎是一件很反常的事情。但是实际上在骨陷窝骨小管系统（lacunocanalicular system） 里流动的骨小管细胞间质液（canalicular fluid） 可以反应出骨组织循环的组成，骨细胞和激素、血液系统中各种循环因子的联系。通过骨硬组织切片在激光共聚焦下的观察也也证实了骨小管系统可以直接和血管相互连接[39].通过小鼠的尾静脉注射普施安红（procion red） ,经过短暂的几分钟红色就可以循环扩散到骨细胞-骨陷窝骨小管系统，研究证实最大70KD的物质可以很容易的从血液系统到达骨陷窝骨小管中。这种骨小管细胞间质液和血液系统的联系使得骨细胞可以暴露于远离器官分泌的循环激素中，同时也为骨细胞分泌的激素和其他蛋白调节介质进入循环系统作用于远离靶器官（distant target organs） 提供了通道。
最近一个非常令人振奋的是发现骨细胞可以产生内分泌因子，所以与之相适应的骨细胞网络结构（osteocyte network） 应该被视为一种内分泌组织，并且发现其在调节机体磷的代谢中起到至关重要的作用。在2000年被发现以来，FGF23一直被视为骨细胞最重要的内分泌因素[40].FGF23最初在丘脑的腹外侧核被发现，但是骨组织的含量最高，主要是由骨细胞产生[41,42],尤其是在低磷血症的时候含量增加。FGF23的一个重要靶器官是肾脏。骨组织和肾脏之间的信号主要取决于循环水平的FGF23的含量，在维持血清磷水平中起到至关重要的作用。FGF23主要降低肾脏中钠磷协同转运蛋白的Na Pi-IIa和Na Pi-IIc的表达，从而抑制肾脏中磷的重吸收。此外过量的FGF23降低1α羟化酶的表达，抑制25羟化维生素D羟化，使25（OH）D不能转化成1,25（OH）2D[41].这种肠腔中1,25（OH,）2D的减少将影响Na Pi-IIb表达，使得小肠中磷的吸收减少，导致低磷血症[43].这种骨细胞和肾脏之间的作用是双向的，1,25（OH）2D在小鼠模型和细胞培养模型中诱导骨细胞FGF23的表达[44],这意味着在骨细胞和肾脏之间可能存在着负反馈效应。
基因打靶技术，尤其是特异性的骨细胞条件性敲除小鼠，揭示了骨细胞对于骨形成和骨吸收的重要作用。尽管这些技术只是揭示了骨细胞的某一个基因在骨代谢中的作用，整体骨细胞网络结构的功能远没有阐述清楚，但是依据骨细胞网络结构破坏的小鼠动物模型的组织学研究，骨细胞网络结构在骨代谢方面的功能逐渐清晰。在生理条件下骨细胞网络结构通过激活破骨细胞促进骨吸收，通过抑制成骨细胞抑制骨形成。骨细胞网络结构对骨量是一个负反馈的作用，而力学刺激可以抑制这种反馈信号，使得骨量增加。
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