Proteolysis Involving Matrix Metalloproteinase 13 (Collagenase‐3) Is Required for Chondrocyte Differentiation That Is Associated with Matrix Mineralization

• Published in: Journal of bone and mineral research 2002-04, Vol.17 (4), p.639-651
• Main Authors: Wu, C. William, Tchetina, Elena V., Mwale, Fackson, Hasty, Karen, Pidoux, Isabelle, Reiner, Agnes, Chen, Jeffrey, Van Wart, Harold E., Poole, A. Robin
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Base Sequence; Biological and medical sciences; calcification; Calcium - metabolism; Carboxylic Acids - pharmacology; cartilage; Cattle; Cbfa1 protein; Cell Differentiation; Cells, Cultured; Chondrocytes - cytology; Cloning, Molecular; Collagen Type II - metabolism; Collagenase 3; collagenases; Collagenases - genetics; Collagenases - metabolism; Enzyme Inhibitors - pharmacology; Extracellular Matrix - metabolism; Fibroblasts - enzymology; Fundamental and applied biological sciences. Psychology; growth plate; Growth Plate - cytology; Growth Plate - enzymology; Hyperostosis - enzymology; Hyperostosis - pathology; hypertrophy; Indoles - pharmacology; Matrix Metalloproteinase 1 - genetics; Matrix Metalloproteinase 13; Matrix Metalloproteinase Inhibitors; matrix metalloproteinases; Minerals - metabolism; Molecular Sequence Data; Neoplasm Proteins; Skeleton and joints; Transcription Factors - drug effects; Transcription Factors - metabolism; Vertebrates: osteoarticular system, musculoskeletal system
• ISSN: 0884-0431; 1523-4681
• DOI: 10.1359/jbmr.2002.17.4.639

Collagenases are involved in cartilage matrix resorption. Using bovine fetal chondrocytes isolated from physeal cartilages and separated into a distinct prehypertrophic subpopulation, we show that in serum‐free culture they elaborate an extracellular matrix and differentiate into hypertrophic chondrocytes. This is characterized by expression of type X collagen and the transcription factor Cbfa1 and increased incorporation of45Ca2+ in the extracellular matrix, which is associated with matrix calcification. Collagenase activity, attributable only to matrix metalloproteinase (MMP) 13 (collagenase‐3), is up‐regulated on differentiation. A nontoxic carboxylate inhibitor of MMP‐13 prevents this differentiation; it suppresses expression of type X collagen, Cbfa1, and MMP‐13 and inhibits increased calcium incorporation in addition to inhibiting degradation of type II collagen in the extracellular matrix. General synthesis of matrix proteins is unaffected. These results suggest that proteolysis involving MMP‐13 is required for chondrocyte differentiation that occurs as part of growth plate development and which is associated with matrix mineralization.