Huang X, Birk D E, Goetinck P F
Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown 02129, USA.
Dev Dyn. 1999 Dec;216(4-5):434-41. doi: 10.1002/(SICI)1097-0177(199912)216:4/5<434::AID-DVDY11>3.0.CO;2-X.
Matrilin-1 (cartilage matrix protein) is a homotrimeric protein that forms collagen-dependent and collagen-independent fibrils in the extracellular matrix of cartilage. In the growth plate of developing long bones, the gene for matrilin-1 is transcribed exclusively by the chondrocytes of the zone of maturation which is situated between the zones of proliferation and hypertrophy. When associated with the cartilage collagen fibril, which consists of collagens type II, IX, and XI, matrilin-1 displays a periodicity of 59.3 nm. Matrilin-1 also interacts with the proteoglycan, aggrecan. Because of its association with the collagen fibril, we tested the hypothesis that matrilin-1 may play a role in collagen fibril formation and cartilage matrix assembly by generating mice with targeted mutations in the matrilin-1 gene. Ultrastructural studies of the cartilage of growth plates of matrilin-1 null mice reveal an abnormal type II collagen fibrillogenesis and fibril organization in the matrix of the zone of maturation. These results represent the first report on the regulation of the heterotypic type II collagen fibril by a non-collagenous protein. The abnormal fibrillogenesis had no obvious effects on skeletal development, on the organization of chondrocytes in the growth plate and on the deposition of aggrecan and the hypertrophic-specific type X collagen in the cartilaginous matrix.
基质金属蛋白酶-1（软骨基质蛋白）是一种同三聚体蛋白，在软骨细胞外基质中形成依赖胶原蛋白和不依赖胶原蛋白的纤维。在发育中的长骨生长板中，基质金属蛋白酶-1基因仅由位于增殖区和肥大区之间的成熟区软骨细胞转录。当与由II型、IX型和XI型胶原蛋白组成的软骨胶原纤维结合时，基质金属蛋白酶-1显示出59.3nm的周期性。基质金属蛋白酶-1还与蛋白聚糖聚集蛋白聚糖相互作用。由于其与胶原纤维的关联，我们通过构建基质金属蛋白酶-1基因靶向突变的小鼠，来测试基质金属蛋白酶-1可能在胶原纤维形成和软骨基质组装中发挥作用的假说。对基质金属蛋白酶-1基因敲除小鼠生长板软骨的超微结构研究显示，成熟区基质中II型胶原纤维形成和纤维组织异常。这些结果代表了关于非胶原蛋白对异型II型胶原纤维调节的首次报道。异常的纤维形成对骨骼发育以及生长板中软骨细胞的组织，以及聚集蛋白聚糖和软骨特异性X型胶原蛋白在软骨基质中的沉积均无明显影响。
