Pacifici M, Iwamoto M, Golden E B, Leatherman J L, Lee Y S, Chuong C M
Department of Anatomy and Histology, School of Dental Medicine, University of Pennsylvania, Philadelphia 19104-6003.
Dev Dyn. 1993 Oct;198(2):123-34. doi: 10.1002/aja.1001980206.
The roles of tenascin in cartilage development and function remain unclear. Based on the observation that tenascin is particularly abundant at the epiphyseal extremities of developing cartilaginous models of long bones in chick and mouse embryo, we tested the hypothesis that tenascin is involved in articular cartilage development. Immunofluorescence analysis revealed that tenascin was first localized in the cell condensation region of Day 4 chick embryo limb buds, where the cartilaginous models form. With further development, tenascin gene expression became indeed restricted to the articular cap of the models. Tenascin persisted in the articular cartilage of postnatal chickens but appeared to decrease with age. The protein was also abundant in embryonic and adult tracheal cartilage rings which, like articular cartilage, persist throughout postnatal life. Similar patterns of tenascin expression were seen in mouse. Using monoclonal antibodies to avian tenascin variants, we found that the bulk of articular cartilage contained the shortest tenascin variant (Tn190), whereas the largest variant (Tn230) was present in tissues associated or interacting with articular cartilage (ligaments and meniscus). The protein and its mRNA, however, were undetectable in growth plate cartilage undergoing maturation and endochondral ossification. This inverse correlation between chondrocyte maturation and tenascin production was corroborated by the finding that tenascin gene expression decreased markedly during maturation of chondrocytes in culture and during formation of a secondary ossification center within the articular cap in vivo. Thus, tenascin is intimately associated with the development of articular cartilage and other permanent cartilages whereas absence or reduced amounts of this matrix protein characterize transient cartilages which undergo maturation and are replaced by bone.
肌腱蛋白在软骨发育和功能中的作用仍不清楚。基于在鸡和小鼠胚胎长骨发育中的软骨模型的骨骺末端肌腱蛋白特别丰富这一观察结果，我们测试了肌腱蛋白参与关节软骨发育的假说。免疫荧光分析显示，肌腱蛋白最初定位于第4天鸡胚肢芽的细胞凝聚区域，软骨模型在此形成。随着进一步发育，肌腱蛋白基因表达确实局限于模型的关节帽。肌腱蛋白在出生后鸡的关节软骨中持续存在，但似乎随着年龄增长而减少。该蛋白在胚胎期和成年期气管软骨环中也很丰富，气管软骨环与关节软骨一样，在出生后整个生命过程中持续存在。在小鼠中也观察到类似的肌腱蛋白表达模式。使用针对禽类肌腱蛋白变体的单克隆抗体，我们发现大部分关节软骨含有最短的肌腱蛋白变体（Tn190），而最大的变体（Tn230）存在于与关节软骨相关或相互作用的组织（韧带和半月板）中。然而，在经历成熟和软骨内成骨的生长板软骨中未检测到该蛋白及其mRNA。软骨细胞成熟与肌腱蛋白产生之间的这种负相关得到了以下发现的证实：在培养的软骨细胞成熟过程中以及在体内关节帽内次级骨化中心形成过程中，肌腱蛋白基因表达明显降低。因此，肌腱蛋白与关节软骨和其他永久性软骨的发育密切相关，而这种基质蛋白的缺失或减少是经历成熟并被骨替代的暂时性软骨的特征。
