Edwards J C, Wilkinson L S, Jones H M, Soothill P, Henderson K J, Worrall J G, Pitsillides A A
Department of Rheumatology, University College London Medical School, UK.
J Anat. 1994 Oct;185 ( Pt 2)(Pt 2):355-67.
During fetal development, cavitation occurs within the primitive skeleton along planes destined to become the articular surfaces of synovial joints. A histochemical study of human fetal limbs was undertaken to identify the cell types involved in this cavitation and the possible role of interactions between cells and extracellular matrix. Cryostat sections were stained with antibodies to CD68, factor VIII related antigen, prolyl hydroxylase, beta 1 integrin, VCAM-1, proliferating cell nuclear antigen, chondroitin-4 sulphate, chondroitin-6-sulphate, hyaluronan synthase and CD44. Similar sections were reacted for uridine diphosphoglucose dehydrogenase (UDPGD) and acid phosphatase activity. Hyaluronan was demonstrated using an aggrecan core protein hyaluronan binding region probe. Macrophages were present prior to cavitation in the periphery of joint interzones but not at the presumptive joint line in the central interzone. Fibroblastic cells were present throughout. Absence of local VCAM-1 expression indicated that cavitation was temporally distinct from full fibroblast-like synoviocyte differentiation. CD44 was expressed by interzone cells at all stages. Staining for hyaluronan and hyaluronan synthase, but not chondroitin sulphates was present in the interzone before and at the time of cavitation. UDPGD activity was increased in a narrow band of cells at the presumptive joint line prior to cavitation. These findings suggest that joint cavitation is dependent on the behaviour of fibroblastic cells and/or adjacent chondrocytes, rather than macrophages. Since UDPGD activity is involved in hyaluronan synthesis, it is proposed that joint cavitation is facilitated by a rise in local hyaluronan concentration in an area of tissue where cohesion is dependent on the interaction between cellular CD44 and extracellular hyaluronan. As proposed by Toole et al. (1984) such a local rise in hyaluronan concentration may lead to a switch from intercellular cohesion to dissociation, leading to tissue cavitation.
在胎儿发育过程中，原始骨骼内沿着注定要成为滑膜关节关节面的平面会发生空化。对人类胎儿肢体进行了一项组织化学研究，以确定参与这种空化的细胞类型以及细胞与细胞外基质之间相互作用的可能作用。冰冻切片用抗CD68、因子VIII相关抗原、脯氨酰羟化酶、β1整合素、血管细胞黏附分子-1（VCAM-1）、增殖细胞核抗原、硫酸软骨素-4、硫酸软骨素-6、透明质酸合酶和CD44的抗体进行染色。类似的切片用于检测尿苷二磷酸葡萄糖脱氢酶（UDPGD）和酸性磷酸酶活性。使用聚集蛋白聚糖核心蛋白透明质酸结合区探针来显示透明质酸。巨噬细胞在关节间区周边空化之前就已存在，但在中央间区的假定关节线处不存在。成纤维细胞全程存在。局部VCAM-1表达的缺失表明空化在时间上与完全的成纤维样滑膜细胞分化不同。CD44在所有阶段的间区细胞中均有表达。在空化之前和空化时，间区存在透明质酸和透明质酸合酶的染色，但不存在硫酸软骨素的染色。在空化之前，假定关节线处的窄带细胞中UDPGD活性增加。这些发现表明关节空化取决于成纤维细胞和/或相邻软骨细胞的行为，而不是巨噬细胞。由于UDPGD活性参与透明质酸合成，因此有人提出，在组织凝聚力依赖于细胞CD44与细胞外透明质酸相互作用的区域，局部透明质酸浓度的升高促进了关节空化。正如Toole等人（1984年）所提出的，这种局部透明质酸浓度升高可能导致从细胞间黏附转变为解离，从而导致组织空化。
