Cartilage matrix resorption in skeletogenesis.

Chondrocytes assemble an extracellular matrix in which the relative composition of type IX versus type II collagen and aggrecan changes during assembly. On maturation and differentiation into hypertrophic cells type IX collagen first loses the NC4 globular domain of the alpha 1(IX) chain that protrudes from the collagen fibril. Subsequently, collagenase 3 (matrix metalloproteinase 13; MMP13) is up-regulated as type X collagen is expressed leading to extensive cleavage and removal of type II collagen and of the remaining COL2 domain of type IX collagen alpha 1(IX) chain. The proteoglycan aggrecan is selectively retained in the extracellular matrix. Inhibition of collagenase leads to arrest of hypertrophy as well as gene expression of MMP13. Thus proteolysis and in particular MMP13 are required for chondrocyte differentiation and for matrix resorption in skeletal development.