Joint Diseases and Matrix Metalloproteinases: A Role for MMP-13

Takaishi, Hironari; Kimura, Tokuhiro; Dalal, Seema S.; Okada, Yasunori; DʼArmiento, Jeanine

doi:10.2174/138920108783497659

Cited by 248 publications

(218 citation statements)

References 56 publications

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“…The MMP‐13 knockout (KO) mice on a 129/Sv genetic background were generated by microinjection of embryonic stem cells into C57BL/6J blastocytes as described before 30, 31. Adult MMP‐13 KO mice were back‐crossed with C57BL/6J strain for at least five times.…”

Section: Methodsmentioning

confidence: 99%

MMP‐13 deletion decreases profibrogenic molecules and attenuates N‐nitrosodimethylamine‐induced liver injury and fibrosis in mice

George

Tsutsumi

Tsuchishima

2017

J Cellular Molecular Medi

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Connective tissue growth factor (CTGF) is involved in inflammation, pathogenesis and progression of liver fibrosis. Matrix metalloproteinase‐13 (MMP‐13) cleaves CTGF and releases several fragments, which are more potent than the parent molecule to induce fibrosis. The current study was aimed to elucidate the significance of MMP‐13 and CTGF and their downstream effects in liver injury and fibrosis. Hepatic fibrosis was induced using intraperitoneal injections of N‐nitrosodimethylamine (NDMA) in doses of 10 μg/g body weight on three consecutive days of each week over a period of 4 weeks in both wild‐type (WT) and MMP‐13 knockout mice. Administration of NDMA resulted in marked elevation of AST, ALT, TGF‐β1 and hyaluronic acid in the serum and activation of stellate cells, massive necrosis, deposition of collagen fibres and increase in total collagen in the liver of WT mice with a significant decrease in MMP‐13 knockout mice. Protein and mRNA levels of CTGF, TGF‐β1, α‐SMA and type I collagen and the levels of MMP‐2, MMP‐9 and cleaved products of CTGF were markedly increased in NDMA‐treated WT mice compared to the MMP‐13 knockout mice. Blocking of MMP‐13 with CL‐82198 in hepatic stellate cell cultures resulted in marked decrease of the staining intensity of CTGF as well as protein levels of full‐length CTGF and its C‐terminal fragments and active TGF‐β1. The data demonstrate that MMP‐13 and CTGF play a crucial role in modulation of fibrogenic mediators and promote hepatic fibrogenesis. Furthermore, the study suggests that blocking of MMP‐13 and CTGF has potential therapeutic implications to arrest liver fibrosis.

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Section: Methodsmentioning

confidence: 99%

MMP‐13 deletion decreases profibrogenic molecules and attenuates N‐nitrosodimethylamine‐induced liver injury and fibrosis in mice

George

Tsutsumi

Tsuchishima

2017

J Cellular Molecular Medi

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“…MMP-13 is expressed by chondrocytes and synovial cells in human OA and RA and is thought to play a critical role in cartilage destruction. The recent development of a MMP-13 knockout mouse has documented the important role played by this enzyme in cartilage formation and further studies under pathological conditions should reveal the function of this enzyme in the progress of the disease (Takaishi et al, 2008) (see Table 6). Several in vitro studies have demonstrated the importance of MMP-13 in human arthritis (Bau et al, 2002;Billinghurst et al, 1997;Mitchell et al, 1996;Reboul et al, 1996).…”

Section: Neoplastic Diseasesmentioning

confidence: 99%

Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes

Sbardella

Fasciglione

Gioia

et al. 2012

Molecular Aspects of Medicine

208

212

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a b s t r a c tHuman matrix metalloproteinases (MMPs) belong to the M10 family of the MA clan of endopeptidases. They are ubiquitarian enzymes, structurally characterized by an active site where a Zn 2+ atom, coordinated by three histidines, plays the catalytic role, assisted by a glutamic acid as a general base. Various MMPs display different domain composition, which is very important for macromolecular substrates recognition. Substrate specificity is very different among MMPs, being often associated to their cellular compartmentalization and/or cellular type where they are expressed. An extensive review of the different MMPs structural and functional features is integrated with their pathological role in several types of diseases, spanning from cancer to cardiovascular diseases and to neurodegeneration. It emerges a very complex and crucial role played by these enzymes in many physiological and pathological processes.

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“…According to Kojima, Hoso, Watanabe, Matsuzaki, Hibino, Sasaki 46 , these changes may be related to the presence of flocculation, corrosion and cracks in the articular cartilage. Taking into consideration the findings of studies by Hadler-Olsen, Fadnes, Sylte, Uhlin-Hansen, Winberg 47 and Takaishi, Kimura, Dalah, Okada, D'Armiento 48 , the changes that were observed in the present study in the LG and EG may have been the result of an increase in the rate of synthesis and the secretion of matrix-degrading enzymes by chondrocytes, as well as the production of metalloproteases that are capable of unfolding collagen and proteoglycans, which release their fragments in the articular fluid, thereby weakening the cartilage matrix. Synovial fluid and the fibrous articular capsule respond to these fragments and other biochemical mediators, such as cytokines and leukotrienes, which leads to changes in the other components of the joint.…”

Section: Discussionmentioning

confidence: 99%

Resistance exercise recovers the structure of cartilage and synovial membrane of the ankle joint of rats after sciatic compression

Vieira

Lovison

Kunz

et al. 2017

Motriz: rev. educ. fis.

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-Aim: to determine the effects of sciatic compression and treatment with resistance exercise on the morphology of the ankle joint of Wistar rats. Methods: 32 male rats, aged 10 ± 1 week, weighing 376±22 grams were divided into the following four groups (n=8/group): CG (control), LG (lesion), EG (exercise) and LEG (lesion and exercise). Three days after sciatic compression, the animals in the EG and LEG were submitted to resistance exercise by climbing stairs (five days/week) for three weeks and a load of 100 grams was added. The exercise was carried out in two sets of ten consecutive ascents of the steps. The ankle joint tissues were analyzed for their morphometry and morphology using light microscopy. Results: Regarding the number of chondrocytes, the LG and EG had more cells in the anterior articular cartilage in the tibia (62 and 43%) and in the talus (57 and 45%) when compared to the CG. In the LEG there was a 25% and 26% reduction of chondrocytes in the anterior cartilage in the tibia and talus when compared to the LG. Changes were observed in the tibia and talus in the LG, with the presence of flocculation, invagination of the subchondral bone, discontinuity of tidemark and pannus covering the subchondral bone in the talus, as well as changes in the synovial membrane. These alterations were minimized in the articular cartilage and synovial membrane in the LEG. Conclusions: exercise restores the tissue morphology of ankle joint in Wistar rats after sciatic compression.

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Joint Diseases and Matrix Metalloproteinases: A Role for MMP-13

Cited by 248 publications

References 56 publications

MMP‐13 deletion decreases profibrogenic molecules and attenuates N‐nitrosodimethylamine‐induced liver injury and fibrosis in mice

MMP‐13 deletion decreases profibrogenic molecules and attenuates N‐nitrosodimethylamine‐induced liver injury and fibrosis in mice

Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes

Resistance exercise recovers the structure of cartilage and synovial membrane of the ankle joint of rats after sciatic compression

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