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骨和软骨一类结缔组织内个别细胞型之间的沟通对于在生理及病理情况下决定这些组织的表型特征是非常重要的。细胞素能调节其它细胞的活性,并在细胞沟通过程中起关键作用。分子生物技术的应用已经使确认特异的细胞素成为可能。这些细胞素以前只是在生物活性的基础上有所明确。这些产物的克隆及顺序已经为细胞素的存在提供正式证据,并可确认它们生物活性的全部情况。这些结果提示:个别的细胞素可以有多方面的生物活性,而众多的细胞素却又可以有共同的功能特性。基于这些结果,“细胞素”这一名称已被普遍应用于诸如白介素、单核细胞素、淋巴细胞素的生长因子或分化因子。细胞素在开始并控制骨组织的生长和发育以及在调节成年机体的骨改建上有重要作用。象在其它结缔组织一样,这些作用是通过旁分泌、自分泌及内分泌机理而得到调节。在骨骼组织中,细胞素还可以通过另外一个机理来调节各种骨的细胞活性。在局部骨内产生的因子以及通过血循环从远处抵达骨的因子被结合进钙化骨基质,在骨改建过程中这些因子被释放出来,并为偶合骨吸收细胞及骨形成细胞提供基础。影响骨组织的主要细胞素包括那些原来被称为单核细胞素或淋巴细胞素的因子,如IL-1、TNT-α、TNF-β及IFN-γ;包括集落刺激因子及生长和分化因子,如TGF-α及TGF-β、IGF-I、PDGF及FGF。虽然个别细胞素的作用很不同,但是可以根据对骨形成及骨吸收特异方面的作用,将个别因子进行分类。最近在阐明细胞素作用的机理方面已取得明显的进展。应用核素配体的结合研究已经确定特异的细胞表面受体,以及它们在骨组织中的分布和性能。各种不同的信号传导途径涉及这些作用的调节。可能的途径还包括内源性细胞内或膜结合底物的磷酸化作用。这种磷酸化作用是由受体-调节酪氨酸特异的蛋白激酶或配体-诱导的第二信使分子(cAMP、二酰基甘油、三磷酸肌醇或钙离子)的释放或产生所引起。有关这些及其它细胞素作用的不同影响和机理的更完整知识,将为在生理及病理情况下调节骨组织内平衡的因素提供更多的了解。
Communication between individual cell types within the connective tissue such as bone and cartilage is important for determining the phenotypic characteristics of these tissues in both physiological and pathological situations. Cytokines regulate the activity of other cells and play a key role in cell communication. The use of molecular biotechnology has made it possible to identify specific cytokines. These cytokines were previously only based on biological activity. The cloning and sequencing of these products has provided formal evidence of the presence of cytokines and can confirm the full extent of their biological activity. These results suggest that individual cytokines can have a wide range of biological activities, while many cytokines may share common functional properties. Based on these results, the term “cytokine” has been widely applied to growth factors such as interleukins, monocytes, lymphokines or differentiation factors. Cytokines play an important role in initiating and controlling the growth and development of bone tissue and in the regulation of bone remodeling in adult humans. Like other connective tissues, these effects are regulated by the paracrine, autocrine and endocrine mechanisms. In bone tissue, cytokines can also regulate the activity of various bone cells through another mechanism. Factors produced in the local bone, as well as factors that reach the bone from afar through the blood circulation, are incorporated into the calcified bone matrix, which are released during bone remodeling and provide the basis for the coupling of bone resorbing cells and bone forming cells. The major cytokines affecting bone tissue include those originally known as monocyte-derived cytokines or lymphokines such as IL-1, TNT-α, TNF-β and IFN-γ; including colony stimulating factor and growth and differentiation factor , Such as TGF-α and TGF-β, IGF-I, PDGF and FGF. Although the effects of individual cytokines vary, individual factors can be classified according to their specific effects on bone formation and bone resorption. Significant progress has recently been made in elucidating the mechanism of cytokines. Binding studies using radionuclide ligands have identified specific cell surface receptors as well as their distribution and performance in bone tissue. A variety of different signaling pathways involve the regulation of these effects. Possible pathways also include the phosphorylation of endogenous intracellular or membrane bound substrates. This phosphorylation is caused by the release or production of receptor-regulated tyrosine-specific protein kinases or ligand-induced second messenger molecules (cAMP, diacylglycerols, inositol trisphosphates or calcium ions). A more complete knowledge of the different effects and mechanisms of these and other cytokines will provide a better understanding of the factors that regulate bone homeostasis under physiological and pathological conditions.