Chondromodulin I is dispensable during enchondral ossification and eye development.

Abstract

Chondromodulin I (chm-I), a type II transmembrane protein, is highly expressed in the avascular zones of cartilage but is downregulated in the hypertrophic region, which is invaded by blood vessels during enchondral ossification. In vitro and in vivo assays with the purified protein have shown chondrocyte-modulating and angiogenesis-inhibiting functions. To investigate chm-I function in vivo, we generated transgenic mice lacking chm-I mRNA and protein. Null mice are viable and fertile and show no morphological changes. No abnormalities in vascular invasion and cartilage development were detectable. No evidence was found for a compensating function of tendin, a recently published homologue highly expressed in tendons and also, at low levels, in cartilage. Furthermore, no differences in the expression of other angiogenic or antiangiogenic factors such as transforming growth factor beta1 (TGF-beta1), TGF-beta2, TGF-beta3, fibroblast growth factor 2, and vascular endothelial growth factor were found. The surprising lack of phenotype in the chm-I-deficient mice suggests either a different function for chm-I in vivo than has been proposed or compensatory changes in uninvestigated angiogenic or angiogenesis-inhibiting factors. Further analysis using double-knockout technology will be necessary to analyze the function of chm-I in the complex process of enchondral ossification.