Osteocytes: a proposed multifunctional bone cell.

Osteocytes: a proposed multifunctional bone cell.
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DOI:
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发表时间:
2002-03
影响因子:
1.9
通讯作者:
L. F. Bonewald
L. F. Bonewald
中科院分区:
医学4区
文献类型:
--
作者:
L. F. Bonewald

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大多数细胞类型被赋予单一功能。破骨细胞具有在体内仅执行一种功能的独特区别-吸收骨。成骨细胞被认为是骨基质生成的主要功能。其他不太明确的细胞类型包括祖细胞和星云细胞类型,其可以在用各种骨吸收细胞因子刺激时支持破骨细胞形成。显然,这些细胞可能有其他功能。骨细胞的定义是描述它的位置-细胞周围的矿化基质-而不是它的功能。对于今年的太阳谷研讨会骨细胞,将提出几个建议的功能。首先,一个普遍的共识是,骨细胞是最有可能敏感的力学转导和翻译机械应变生化信号。在机械应变的性质、生化信号的形式、靶细胞或骨细胞的活力状态上不存在共识。其次,它也提出,这种细胞是令人难以置信的适应性和表达可塑性,以响应机械刺激。换句话说,这种细胞可以在其他骨因子(如激素和骨因子)存在的情况下重新调整其对应变的反应。第三,它也将提出,骨细胞保持全身矿物质的稳态,通过调节矿物质的释放和沉积在巨大的表面积上,这些细胞与周围的基质界面。虽然骨细胞是终末分化的成骨细胞,但它们似乎具有与其前身不同的特性。骨细胞生物学家装载了大量的骨合成代谢和分解代谢因子,正在研究这些因子对骨细胞的表达和影响。受过数学建模训练的工程师已经生成了新的应变和连通性模型,以供测试。骨细胞的独特形态表明,这些细胞中的细胞骨架可能与成骨细胞和其他细胞类型不同。骨细胞可能由不同的亚群组成;一些具有甲状旁腺激素(PTH)受体,另一些仅表达羧基末端PTH受体,表明不同的功能和反应。骨细胞可能通过谷氨酸受体样机制、钙离子流入、间隙连接对应变迅速作出反应,而通过产生小分子和因子的反应较慢。应变可以采取基底拉伸和/或流体流动的形式。骨细胞可以与其他骨细胞和/或骨表面细胞如衬里细胞、基质细胞、成骨细胞和/或破骨细胞及其前体细胞通讯。骨细胞的活力状态可以决定从这些细胞发出的信号的类型。如果细胞被剥夺了氧气或营养,凋亡细胞可能会发出信号,开始吸收。如果细胞和/或它们的树突状突起被微损伤撕裂或撕裂,它们可能会发出再吸收和形成的信号。如果这些理论中的大多数是正确的,那么骨细胞是“聪明”的细胞,即使在其死亡和死亡时也可以指导或协调骨吸收和骨形成细胞。
Most cell types are ascribed a single function. The osteoclast holds the unique distinction of performing only one function in the body - that of resorbing bone. The osteoblast has been ascribed the major function of bone matrix production. Other less well-defined cell types include progenitor cells and the nebulous cell type that can support osteoclast formation upon stimulation with various bone resorbing cytokines. Obviously, these cells could have other functions. The definition of an osteocyte is descriptive of its location - cells surrounded by mineralized matrix - not its function. For this year's Sun Valley Workshop on osteocytes, several proposed functions will be presented. First, a general consensus exists that osteocytes are most likely sensitive to mechanotransduction and translate mechanical strain into biochemical signals. Consensus does not exist on the nature of the mechanical strain, the form of the biochemical signals, the target cell(s), or the viability status of the osteocyte. Second, it is also proposed that this cell is incredibly adaptable and expresses plasticity in response to mechanical stimuli. In other words, this cell can readjust its responses to strain in the presence of other bone agents such as hormones and bone factors. Third, it will also be presented that osteocytes maintain systemic mineral homeostasis by regulating mineral release and deposition over the enormous surface area over which these cells interface with the surrounding matrix. Although osteocytes are terminally differentiated osteoblasts, they appear to have separate and distinct properties from their predecessors. Bone cell biologists loaded with an arsenal of bone anabolic and catabolic factors are examining the expression and effects of these factors on osteocytes. Engineers trained in mathematical modeling have generated new models of strain and connectivity to be tested. The unique morphology of osteocytes suggests that the cytoskeleton in these cells may function differently from osteoblasts and other cell types. Osteocytes may consist of different subpopulations; some that possess receptors for parathyroid hormone (PTH) and others that only express receptors for carboxyl terminal PTH suggesting different functions and responses. Osteocytes may respond rapidly to strain through glutamate receptor-like mechanisms, through calcium influxes, through gap junctions, and less rapidly through the production of small molecules and factors. Strain may take the form of substrate stretching and/or fluid flow. Osteocytes may communicate with other osteocytes and/or bone surface cells such as lining cells, stromal cells, osteoblasts, and/or osteoclasts and their precursors. The viability status of the osteocyte may determine the type of signals sent from these cells. If the cells are deprived of oxygen or nutrients, the apoptotic cells may send signals for initiation of resorption. If the cells and/or their dendritic process are ripped or torn by microdamage, they may send signals of both resorption and formation. If the majority of these theories are correct, then the osteocyte is the 'smart' cell that can direct or orchestrate the bone resorbing and bone forming cells even in its death and dying.