Department of Pathology & Cell Biology, University of South Florida College of Medicine, Tampa, FL 33612-4799, USA.
Matrix Biol. 2011 Jan;30(1):53-61. doi: 10.1016/j.matbio.2010.10.001. Epub 2010 Oct 14.
Tendons are composed of fibroblasts and collagen fibrils. The fibrils are organized uniaxially and grouped together into fibers. Collagen VI is a non-fibrillar collagen expressed in developing and adult tendons. Human collagen VI mutations result in muscular dystrophy, joint hyperlaxity and contractures. The purpose of this study is to determine the functional roles of collagen VI in tendon matrix assembly. During tendon development, collagen VI was expressed throughout the extracellular matrix, but enriched around fibroblasts and their processes. To analyze the functional roles of collagen VI a mouse model with a targeted inactivation of Col6a1 gene was utilized. Ultrastructural analysis of Col6a1-/- versus wild type tendons demonstrated disorganized extracellular micro-domains and associated collagen fibers in the Col6a1-/- tendon. In Col6a1-/- tendons, fibril structure and diameter distribution were abnormal compared to wild type controls. The diameter distributions were shifted significantly toward the smaller diameters in Col6a1-/- tendons compared to controls. An analysis of fibril density (number/μm(2)) demonstrated a ~2.5 fold increase in the Col6a1-/- versus wild type tendons. In addition, the fibril arrangement and structure were aberrant in the peri-cellular regions of Col6a1-/- tendons with frequent very large fibrils and twisted fibrils observed restricted to this region. The biomechanical properties were analyzed in mature tendons. A significant decrease in cross-sectional area was observed. The percent relaxation, maximum load, maximum stress, stiffness and modulus were analyzed and Col6a1-/- tendons demonstrated a significant reduction in maximum load and stiffness compared to wild type tendons. An increase in matrix metalloproteinase activity was suggested in the absence of collagen VI. This suggests alterations in tenocyte expression due to disruption of cell-matrix interactions. The changes in expression may result in alterations in the peri-cellular environment. In addition, the absence of collagen VI may alter the sequestering of regulatory molecules such as leucine rich proteoglycans. These changes would result in dysfunctional regulation of tendon fibrillogenesis indirectly mediated by collagen VI.
肌腱由成纤维细胞和胶原纤维组成。纤维呈单轴排列，并聚集在一起形成纤维。胶原 VI 是非纤维胶原，在发育中和成人肌腱中表达。人类胶原 VI 突变导致肌肉营养不良、关节过度伸展和挛缩。本研究的目的是确定胶原 VI 在肌腱基质组装中的功能作用。在肌腱发育过程中，胶原 VI 表达于整个细胞外基质，但在成纤维细胞及其突起周围富集。为了分析胶原 VI 的功能作用，利用 Col6a1 基因靶向失活的小鼠模型进行了分析。Col6a1-/-与野生型肌腱的超微结构分析表明，Col6a1-/-肌腱的细胞外微区和相关胶原纤维排列紊乱。与野生型对照相比，Col6a1-/-肌腱中的原纤维结构和直径分布异常。在 Col6a1-/-肌腱中，直径分布向较小直径显著偏移。胶原纤维密度（每 μm²的纤维数量）分析表明，Col6a1-/-肌腱中的纤维密度比野生型对照增加了约 2.5 倍。此外，Col6a1-/-肌腱的细胞周区胶原纤维排列和结构异常，经常观察到非常大的纤维和扭曲的纤维仅限于该区域。成熟肌腱的生物力学特性进行了分析。观察到横截面积显著减小。分析了百分比松弛、最大载荷、最大应力、刚度和模量，与野生型肌腱相比，Col6a1-/-肌腱的最大载荷和刚度显著降低。由于细胞-基质相互作用的破坏，胶原 VI 缺失可能导致基质金属蛋白酶活性增加。这表明由于细胞-基质相互作用的破坏，肌腱细胞表达发生改变。表达的变化可能导致细胞外环境的改变。此外，胶原 VI 的缺失可能会改变调节分子（如富含亮氨酸的蛋白聚糖）的隔离。这些变化将导致肌腱原纤维生成的间接功能调节失常，这一过程由胶原 VI 介导。
