Differential expression of lumican and fibromodulin regulate collagen fibrillogenesis in developing mouse tendons

Collagen fibrillogenesis is finely regulated during development of tissue-s pecific extracellular matrices. The role(s) of a leucine-rich repeat protei n sub-family in the regulation of fibrillogenesis during tendon development were defined. Lumican-, fibromodulin-, and double-deficient mice demonstra ted disruptions in fibrillogenesis, With development, the amount of lumican decreases to barely detectable levels while fibromodulin increases signifi cantly, and these changing patterns may regulate this process. Electron mic roscopic analysis demonstrated structural abnormalities in the fibrils and alterations in the progression through different assembly steps. In lumican -deficient tendons, alterations were observed early and the mature tendon w as nearly normal. Fibromodulin-deficient tendons were comparable with the l umican-null in early developmental periods and acquired a severe phenotype by maturation. The double-deficient mice had a phenotype that was additive early and comparable with the fibromodulin-deficient mice at maturation. Th erefore, lumican and fibromodulin both influence initial assembly of interm ediates and the entry into fibril growth, while fibromodulin facilitates th e progression through growth steps leading to mature fibrils. The observed increased ratio of fibromodulin to lumican and a competition for the same b inding site could mediate these transitions. These studies indicate that lu mican and fibromodulin have different developmental stage and leucine-rich repeat protein specific functions in the regulation of fibrillogenesis.