Mice lacking matrilin-1 (cartilage matrix protein) have alterations in type II collagen fibrillogenesis and fibril organization.

Abstract

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.