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Gene Review

Mmp13  -  matrix metallopeptidase 13

Mus musculus

Synonyms: Clg, Collagenase 3, Collagenase-3, MMP-13, Matrix metalloproteinase-13, ...
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Disease relevance of Mmp13


High impact information on Mmp13

  • A pericellular collagenase directs the 3-dimensional development of white adipose tissue [7].
  • Collagenase expression in the lungs of transgenic mice causes pulmonary emphysema [8].
  • This pathology is strikingly similar to the morphological changes observed in human emphysema and therefore implicates interstitial collagenase as a possible etiological agent in the disease process [8].
  • We demonstrate that c-Jun and Jun-B nevertheless differ markedly in their ability to activate AP-1 responsive genes. c-Jun is an efficient activator of the c-jun and collagenase promoters, which contain a single TRE; Jun-B is not [9].
  • In intact cells, the active site of the 16S acetylcholinesterase is protected by a membrane-impermeable inhibitor, and this form of the enzyme can be removed by treatment of the cells with collagenase [10].

Chemical compound and disease context of Mmp13


Biological context of Mmp13

  • The severity of the Mmp13- null growth plate phenotype increased until about 5 weeks and completely resolved by 12 weeks of age [16].
  • On the basis of these transcriptional regulation studies, together with the potent proteolytic activity of collagenase 3 on diverse collagenous and noncollagenous bone and cartilage components, we proposed that this enzyme may play a key role in the process of bone formation and remodeling [1].
  • Upregulation of fibrogenic markers, for example, transforming growth factor beta1 (TGF-beta1), was also significantly suppressed in livers of MMP-13-deficient mice versus in WT mice [2].
  • In Gadd45beta(-/-) mouse embryos, defective mineralization and decreased bone growth accompanied deficient Mmp-13 and Col10a1 gene expression in the hypertrophic zone [17].
  • During wound healing, MMP-13 and TNFalpha were stimulated to an even higher level, suggesting they are regulated by multiple factors [18].

Anatomical context of Mmp13


Associations of Mmp13 with chemical compounds


Physical interactions of Mmp13


Enzymatic interactions of Mmp13


Co-localisations of Mmp13


Regulatory relationships of Mmp13


Other interactions of Mmp13

  • Whereas MMP-13 was transiently expressed mainly in the cells clustering in the periportal areas, MMP-9 expression and enzymatic activity were detected over the resolution process in several different kinds of cells located in the portal areas and along the fibrous septa [36].
  • Like in man and rat, the expressions of collagenase I, stromelysin-1, and stromelysin-2 are regulated by the tumor promoter 12-O-tetradecanoyl-phorbol 13-acetate and by UV irradiation, but not by cAMP [37].
  • The sites of induced collagenase I expression correlate with the sites of Fos-induced long-term cellular alterations in transgenic mice including bone remodeling and T cell development [37].
  • The expression of MMP-13 and DDR-2 protein and the amount of degraded type II collagen were higher in the knee joints of Col9a1(-/-) mice than in their wild-type littermates at the age of 6 months [38].
  • Both AP-1 and Cbfa1-like factors are required for the induction of interstitial collagenase by parathyroid hormone [39].

Analytical, diagnostic and therapeutic context of Mmp13


  1. Collagenase 3 is a target of Cbfa1, a transcription factor of the runt gene family involved in bone formation. Jiménez, M.J., Balbín, M., López, J.M., Alvarez, J., Komori, T., López-Otín, C. Mol. Cell. Biol. (1999) [Pubmed]
  2. Loss of MMP 13 attenuates murine hepatic injury and fibrosis during cholestasis. Uchinami, H., Seki, E., Brenner, D.A., D'Armiento, J. Hepatology (2006) [Pubmed]
  3. The effects of selective inhibitors of matrix metalloproteinases (MMPs) on bone resorption and the identification of MMPs and TIMP-1 in isolated osteoclasts. Hill, P.A., Murphy, G., Docherty, A.J., Hembry, R.M., Millican, T.A., Reynolds, J.J., Meikle, M.C. J. Cell. Sci. (1994) [Pubmed]
  4. Cumulative influence of matrix metalloproteinase-1 and -2 in the migration of melanoma cells within three-dimensional type I collagen lattices. Ntayi, C., Lorimier, S., Berthier-Vergnes, O., Hornebeck, W., Bernard, P. Exp. Cell Res. (2001) [Pubmed]
  5. Scar-associated macrophages are a major source of hepatic matrix metalloproteinase-13 and facilitate the resolution of murine hepatic fibrosis. Fallowfield, J.A., Mizuno, M., Kendall, T.J., Constandinou, C.M., Benyon, R.C., Duffield, J.S., Iredale, J.P. J. Immunol. (2007) [Pubmed]
  6. Matrix metalloproteinase 13-deficient mice are resistant to osteoarthritic cartilage erosion but not chondrocyte hypertrophy or osteophyte development. Little, C.B., Barai, A., Burkhardt, D., Smith, S.M., Fosang, A.J., Werb, Z., Shah, M., Thompson, E.W. Arthritis Rheum. (2009) [Pubmed]
  7. A pericellular collagenase directs the 3-dimensional development of white adipose tissue. Chun, T.H., Hotary, K.B., Sabeh, F., Saltiel, A.R., Allen, E.D., Weiss, S.J. Cell (2006) [Pubmed]
  8. Collagenase expression in the lungs of transgenic mice causes pulmonary emphysema. D'Armiento, J., Dalal, S.S., Okada, Y., Berg, R.A., Chada, K. Cell (1992) [Pubmed]
  9. Jun-B differs in its biological properties from, and is a negative regulator of, c-Jun. Chiu, R., Angel, P., Karin, M. Cell (1989) [Pubmed]
  10. Association of the synaptic form of acetylcholinesterase with extracellular matrix in cultured mouse muscle cells. Inestrosa, N.C., Silberstein, L., Hall, Z.W. Cell (1982) [Pubmed]
  11. Blockade of advanced glycation end-product formation restores ischemia-induced angiogenesis in diabetic mice. Tamarat, R., Silvestre, J.S., Huijberts, M., Benessiano, J., Ebrahimian, T.G., Duriez, M., Wautier, M.P., Wautier, J.L., Lévy, B.I. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  12. Initiation of osteoclast bone resorption by interstitial collagenase. Holliday, L.S., Welgus, H.G., Fliszar, C.J., Veith, G.M., Jeffrey, J.J., Gluck, S.L. J. Biol. Chem. (1997) [Pubmed]
  13. Tumor necrosis factor receptor deficiency alters matrix metalloproteinase 13/tissue inhibitor of metalloproteinase 1 expression in murine silicosis. Ortiz, L.A., Lasky, J., Gozal, E., Ruiz, V., Lungarella, G., Cavarra, E., Brody, A.R., Friedman, M., Pardo, A., Selman, M. Am. J. Respir. Crit. Care Med. (2001) [Pubmed]
  14. Inhibitory effects of oleic and docosahexaenoic acids on lung metastasis by colon-carcinoma-26 cells are associated with reduced matrix metalloproteinase-2 and -9 activities. Suzuki, I., Iigo, M., Ishikawa, C., Kuhara, T., Asamoto, M., Kunimoto, T., Moore, M.A., Yazawa, K., Araki, E., Tsuda, H. Int. J. Cancer (1997) [Pubmed]
  15. Granuloma collagenase and EDTA-sensitive neutral protease production in hepatic murine schistosomiasis. Takahashi, S., Simpser, E. Hepatology (1981) [Pubmed]
  16. Altered endochondral bone development in matrix metalloproteinase 13-deficient mice. Stickens, D., Behonick, D.J., Ortega, N., Heyer, B., Hartenstein, B., Yu, Y., Fosang, A.J., Schorpp-Kistner, M., Angel, P., Werb, Z. Development (2004) [Pubmed]
  17. A novel role for GADD45beta as a mediator of MMP-13 gene expression during chondrocyte terminal differentiation. Ijiri, K., Zerbini, L.F., Peng, H., Correa, R.G., Lu, B., Walsh, N., Zhao, Y., Taniguchi, N., Huang, X.L., Otu, H., Wang, H., Wang, J.F., Komiya, S., Ducy, P., Rahman, M.U., Flavell, R.A., Gravallese, E.M., Oettgen, P., Libermann, T.A., Goldring, M.B. J. Biol. Chem. (2005) [Pubmed]
  18. Cyclophilin C-associated protein is a mediator for fibronectin fragment-induced matrix metalloproteinase-13 expression. Kong, W., Longaker, M.T., Lorenz, H.P. J. Biol. Chem. (2004) [Pubmed]
  19. Critical roles for collagenase-3 (Mmp13) in development of growth plate cartilage and in endochondral ossification. Inada, M., Wang, Y., Byrne, M.H., Rahman, M.U., Miyaura, C., López-Otín, C., Krane, S.M. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  20. Tumor cell-derived collagenase-stimulatory factor increases expression of interstitial collagenase, stromelysin, and 72-kDa gelatinase. Kataoka, H., DeCastro, R., Zucker, S., Biswas, C. Cancer Res. (1993) [Pubmed]
  21. Ascorbic acid induces collagenase-1 in human periodontal ligament cells but not in MC3T3-E1 osteoblast-like cells: potential association between collagenase expression and changes in alkaline phosphatase phenotype. Shiga, M., Kapila, Y.L., Zhang, Q., Hayami, T., Kapila, S. J. Bone Miner. Res. (2003) [Pubmed]
  22. Effects of retinoic acid on the differentiation of chondrogenic progenitor cells, ATDC5. Kirimoto, A., Takagi, Y., Ohya, K., Shimokawa, H. J. Med. Dent. Sci. (2005) [Pubmed]
  23. Postnatal expression in hyaline cartilage of constitutively active human collagenase-3 (MMP-13) induces osteoarthritis in mice. Neuhold, L.A., Killar, L., Zhao, W., Sung, M.L., Warner, L., Kulik, J., Turner, J., Wu, W., Billinghurst, C., Meijers, T., Poole, A.R., Babij, P., DeGennaro, L.J. J. Clin. Invest. (2001) [Pubmed]
  24. A regulatory cascade involving retinoic acid, Cbfa1, and matrix metalloproteinases is coupled to the development of a process of perichondrial invasion and osteogenic differentiation during bone formation. Jiménez, M.J., Balbín, M., Alvarez, J., Komori, T., Bianco, P., Holmbeck, K., Birkedal-Hansen, H., López, J.M., López-Otín, C. J. Cell Biol. (2001) [Pubmed]
  25. Mechanical strain induces collagenase-3 (MMP-13) expression in MC3T3-E1 osteoblastic cells. Yang, C.M., Chien, C.S., Yao, C.C., Hsiao, L.D., Huang, Y.C., Wu, C.B. J. Biol. Chem. (2004) [Pubmed]
  26. Collagenase is expressed by rabbit VX2 tumour cells in syngeneic and xenogeneic hosts. Gavrilovic, J., Hembry, R.M., Reynolds, J.J., Murphy, G. Matrix (1989) [Pubmed]
  27. c-Jun N-terminal kinase is required for metalloproteinase expression and joint destruction in inflammatory arthritis. Han, Z., Boyle, D.L., Chang, L., Bennett, B., Karin, M., Yang, L., Manning, A.M., Firestein, G.S. J. Clin. Invest. (2001) [Pubmed]
  28. Prolactin receptor on dissociated mammary epithelial cells at different stages of development. Sakai, S., Enami, J., Nandi, S., Banerjee, M.R. Mol. Cell. Endocrinol. (1978) [Pubmed]
  29. Collagenase-3 binds to a specific receptor and requires the low density lipoprotein receptor-related protein for internalization. Barmina, O.Y., Walling, H.W., Fiacco, G.J., Freije, J.M., López-Otín, C., Jeffrey, J.J., Partridge, N.C. J. Biol. Chem. (1999) [Pubmed]
  30. DNA binding of Jun and Fos bZip domains: homodimers and heterodimers induce a DNA conformational change in solution. John, M., Leppik, R., Busch, S.J., Granger-Schnarr, M., Schnarr, M. Nucleic Acids Res. (1996) [Pubmed]
  31. Antitumor effects of the molecule-downsized immunoconjugate composed of lidamycin and Fab' fragment of monoclonal antibody directed against type IV collagenase. Fengqiang, W., Boyang, S., Yongsu, Z. Sci. China, C, Life Sci. (2004) [Pubmed]
  32. Role of matrix metalloproteinases and their inhibition in cutaneous wound healing and allergic contact hypersensitivity. Pilcher, B.K., Wang, M., Qin, X.J., Parks, W.C., Senior, R.M., Welgus, H.G. Ann. N. Y. Acad. Sci. (1999) [Pubmed]
  33. Mmp-9 deficiency enhances collagenase-induced intracerebral hemorrhage and brain injury in mutant mice. Tang, J., Liu, J., Zhou, C., Alexander, J.S., Nanda, A., Granger, D.N., Zhang, J.H. J. Cereb. Blood Flow Metab. (2004) [Pubmed]
  34. Coordinate expression of matrix metalloproteinase family members in the uterus of normal, matrilysin-deficient, and stromelysin-1-deficient mice. Rudolph-Owen, L.A., Hulboy, D.L., Wilson, C.L., Mudgett, J., Matrisian, L.M. Endocrinology (1997) [Pubmed]
  35. Collagenase-3 (MMP-13) and integral membrane protein 2a (Itm2a) are marker genes of chondrogenic/osteoblastic cells in bone formation: sequential temporal, and spatial expression of Itm2a, alkaline phosphatase, MMP-13, and osteocalcin in the mouse. Tuckermann, J.P., Pittois, K., Partridge, N.C., Merregaert, J., Angel, P. J. Bone Miner. Res. (2000) [Pubmed]
  36. Bone marrow-derived cells express matrix metalloproteinases and contribute to regression of liver fibrosis in mice. Higashiyama, R., Inagaki, Y., Hong, Y.Y., Kushida, M., Nakao, S., Niioka, M., Watanabe, T., Okano, H., Matsuzaki, Y., Shiota, G., Okazaki, I. Hepatology (2007) [Pubmed]
  37. Phenotypic alterations in fos-transgenic mice correlate with changes in Fos/Jun-dependent collagenase type I expression. Regulation of mouse metalloproteinases by carcinogens, tumor promoters, cAMP, and Fos oncoprotein. Gack, S., Vallon, R., Schaper, J., Rüther, U., Angel, P. J. Biol. Chem. (1994) [Pubmed]
  38. Pathogenesis of osteoarthritis-like changes in the joints of mice deficient in type IX collagen. Hu, K., Xu, L., Cao, L., Flahiff, C.M., Brussiau, J., Ho, K., Setton, L.A., Youn, I., Guilak, F., Olsen, B.R., Li, Y. Arthritis Rheum. (2006) [Pubmed]
  39. Both AP-1 and Cbfa1-like factors are required for the induction of interstitial collagenase by parathyroid hormone. Porte, D., Tuckermann, J., Becker, M., Baumann, B., Teurich, S., Higgins, T., Owen, M.J., Schorpp-Kistner, M., Angel, P. Oncogene (1999) [Pubmed]
  40. Expression of interstitial collagenase during skeletal development of the mouse is restricted to osteoblast-like cells and hypertrophic chondrocytes. Gack, S., Vallon, R., Schmidt, J., Grigoriadis, A., Tuckermann, J., Schenkel, J., Weiher, H., Wagner, E.F., Angel, P. Cell Growth Differ. (1995) [Pubmed]
  41. Frog PNKT-4B cells express specific extracellular matrix-degrading enzymes and cytokines correlated with an invasive phenotype. Strissel, K.J., Tessier, M.J., Shams, N.B., Grabbe, S., Gross, J., Fini, M.E. J. Exp. Zool. (1997) [Pubmed]
  42. Transforming growth factor beta1 stimulates contrasting responses in metastatic versus primary mouse prostate cancer-derived cell lines in vitro. Sehgal, I., Baley, P.A., Thompson, T.C. Cancer Res. (1996) [Pubmed]
  43. Cell surface-bound collagenase-1 and focal substrate degradation stimulate the rear release of motile vascular smooth muscle cells. Li, S., Chow, L.H., Pickering, J.G. J. Biol. Chem. (2000) [Pubmed]
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