CCN1 and CCN2 are members of a family of 6 structurally related matricellular proteins that serve regulatory roles in cell proliferation, differentiation and survival through their interaction with integrins.
In aim 1, we propose to investigate the nature of cartilage defects in CCN2 mutant mice by examining the ultrastructure of the growth plate and looking at levels of gene expression in Ccn2 -/- chondrocytes.
In aim 2, we will examine the mRNA and protein distribution of CCN1 and CCN2 in cartilage and look at cartilage specific loss of CCN1. Our goal is to determine whether CCN1 and CCN2 are expressed in the same regions during cartilage development, and whether they have identical function. To test this, in aim 3, we make CCN1/CCN2 double mutants. Understanding the extent to which Ccn1 and Ccn2 have overlapping vs. distinct roles in chondrogenesis is essential to understanding the diverse array of cellular activities these proteins regulate during chondrogenesis and the extent to which they transduce distinct signals as well as providing valuable insight into how we might use the CCN1 and CCN2 to treat arthritis.
