MMP13

Official Full Name

matrix metallopeptidase 13

Organism

Homo sapiens

GeneID

4322

Background

This gene encodes a member of the peptidase M10 family of matrix metalloproteinases (MMPs). Proteins in this family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. The encoded preproprotein is proteolytically processed to generate the mature protease. This protease cleaves type II collagen more efficiently than types I and III. It may be involved in articular cartilage turnover and cartilage pathophysiology associated with osteoarthritis. Mutations in this gene are associated with metaphyseal anadysplasia. This gene is part of a cluster of MMP genes on chromosome 11. [provided by RefSeq, Jan 2016]

Synonyms

CLG3; MDST; MANDP1; MMP-13;

Bio Chemical Class

Peptidase

Protein Sequence

MHPGVLAAFLFLSWTHCRALPLPSGGDEDDLSEEDLQFAERYLRSYYHPTNLAGILKENAASSMTERLREMQSFFGLEVTGKLDDNTLDVMKKPRCGVPDVGEYNVFPRTLKWSKMNLTYRIVNYTPDMTHSEVEKAFKKAFKVWSDVTPLNFTRLHDGIADIMISFGIKEHGDFYPFDGPSGLLAHAFPPGPNYGGDAHFDDDETWTSSSKGYNLFLVAAHEFGHSLGLDHSKDPGALMFPIYTYTGKSHFMLPDDDVQGIQSLYGPGDEDPNPKHPKTPDKCDPSLSLDAITSLRGETMIFKDRFFWRLHPQQVDAELFLTKSFWPELPNRIDAAYEHPSHDLIFIFRGRKFWALNGYDILEGYPKKISELGLPKEVKKISAAVHFEDTGKTLLFSGNQVWRYDDTNHIMDKDYPRLIEEDFPGIGDKVDAVYEKNGYIYFFNGPIQFEYSIWSNRIVRVMPANSILWC

Open

Disease

Corneal disease, Hepatitis virus infection, Pain, Postoperative inflammation, Rheumatoid arthritis, Solid tumour/cancer

Approved Drug

Clinical Trial Drug

3 +

Discontinued Drug

2 +

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Detailed Information

Matrix metalloprotease (MMP-13) was cloned from breast cancer cells in 1994 and has important bone biological roles in the development of cartilage tissue growth and calcification centers. MMP-13 is the main enzyme that promotes its degradation, which irreversibly degrades type II collagen, causing destruction of articular cartilage. MMP-13 can be affected by a variety of factors, such as IL1β, TNF-α, Runx2. The can induce the expression of MMP-13. Hypomethylation of the MMP-13 promoter region also induces its expression, but its expression can be reduced by inhibiting histone acetylation. In addition, microRNAs can also reduce MMP-13 expression through gene regulation. Up-regulation of MMP-13 causes degeneration of cartilage, which in turn promotes the progression of arthritis.

MMP13 Figure 1. Regulatory network of MMP-13 in OA chondrocytes. (Li, H., et al. 2017)

MMP-13 and Osteoarthritis

Osteoarthritis (OA) is the most common form of arthritis, usually characterized by joint pain and dysfunction, which seriously affects the quality of life of patients. MMP-13 can preferentially degrade type II collagen to make it a major protease for cartilage degradation. In addition, it can degrade proteoglycans, type IV and type IX collagen, osteonectin and cartilage basement glycans, which are also components of the cartilage matrix. MMP-13 is rarely seen in normal adult tissues, but is more expressed in articular cartilage of OA patients. Compared with other MMPs, MMP-13 expression is more confined in connective tissue. Clinical studies have found that MMP-13 is highly expressed in patients with articular cartilage destruction, suggesting that increased MMP-13 may be associated with cartilage degradation. Studies have also found that transgenic mice overexpressing MMP-13 show a spontaneous OA-like articular cartilage degradation phenotype, while MMP-13 gene knockout prevents joint cartilage degradation.

Studies have found that down-regulation of MMP-13 expression may alter phenotype in mice deficient in fibroblasts. Studies have shown that up-regulation of MMP-13 transcription can affect cartilage homeostasis, leading to joint disease, while down-regulation of MMP-13 expression and activation can achieve therapeutic OA. The intrinsic Smad3 gene of chondrocytes maintains articular cartilage by inhibiting the expression of Runx-2-inducible MMP-13, preventing OA production. Studies have found that selective MMP-13 inhibitors completely inhibit the degradation of type II collagen in bovine knee joint grafts and inhibit the degradation of 80% of human OA cartilage. Moreover, a study has shown that MMP-13 inhibitors are effective in reducing articular cartilage loss in a wound-mediated knee OA mouse model. The study also found that some inhibitors that do not act on MMP-13 itself. For example, the purchase of Juni (vitamin) can be used to inhibit MMP-13 by inhibiting the induction and activation of MMP -13 gene levels by IL-1β.

MMP-13 and Periodontitis

MMP-13 is closely related to the rapid transformation of collagen fibers in tissues. Since MMP-13 is the primary expression of collagenase in epithelial tissues, it is also expressed in inflammatory periodontal connective tissue cells. Therefore, MMP-13 plays an important role in the transformation of epithelial tissue into connective tissue in the presence of oral mucosal inflammation. Studies have shown that the quality of collagenase and gelase in gingival crevicular fluid (GCF) is positively correlated with the severity of periodontal disease, while MMP-8 and 9 play a leading role in chronic periodontitis. In contrast, MMP-13 accounts for only 3% to 4% of the same type of inflammatory GCF, while MMP-1 is basically absent. However, some studies have found that human osteoblasts produce MMP-13 instead of MMP-8. MMP-13 activates osteoblasts to produce precursor MMP-9, which mediates a series of periodontal tissue destruction by MMP-8 and MMP-9.

References:

Li, H. , Wang, D. , Yuan, Y. , & Min, J. . (2017). New insights on the mmp-13 regulatory network in the pathogenesis of early osteoarthritis. Arthritis Research & Therapy, 19(1), 248.
Liu, Q. , Zhang, X. , Hu, X. , Dai, L. , Fu, X. , & Zhang, J. , et al. (2016). Circular rna related to the chondrocyte ecm regulates mmp13 expression by functioning as a mir-136 ‘sponge’ in human cartilage degradation. Scientific Reports, 6, 22572.
Sheibani, S. , Mahmoudian, R. A. , Abbaszadegan, M. R. , Chamani, J. , Memar, B. , & Gholamin, M. . (2017). Expression analysis of matrix metalloproteinase-13 in human gastric cancer in the presence of helicobacter pylori infection. Cancer Biomarkers, 18(4), 349-356.

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