Dupuytren's disease and frozen shoulder induced by treatment with a matrix metalloproteinase inhibitor

Hutchinson, J. W.; Tierney, Gillian; Parsons, S. L.; Davis, T. R. C.

doi:10.1302/0301-620x.80b5.8464

Cited by 158 publications

(81 citation statements)

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“…In the present study protein levels of the MMPs and TIMPs were not measured. In addition, Hutchinson et al 27 did not confirm decreased MMP:TIMP ratios (mRNA or protein) in the pathologic tissue. Further work is required to understand which mechanisms may be active.…”

Section: Discussionmentioning

confidence: 94%

“…A decreasing MMP:TIMP ratio would support ineffective degradation, and is consistent with a report regarding contracture phenomena and synthetic MMP inhibitors. Hutchinson et al 27 indicated that frozen shoulder and Dupuytren's contracture of the hand developed in 6 of 12 patients with inoperable gastric carcinoma who were given a synthetic MMP inhibitor for greater than 1 month. The inhibitor treatment would be expected to lead to a reduction in the MMP:TIMP ratio.…”

Section: Discussionmentioning

confidence: 99%

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Joint capsule matrix turnover in a rabbit model of chronic joint contractures: Correlation with human contractures

Hildebrand

Zhang

Hart

2006

Journal Orthopaedic Research

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To evaluate changes in matrix molecules of the joint capsule, the right knees of 24 skeletally mature female NZW rabbits were immobilized while the contralateral limb served as an unoperated control. The immobilization was discontinued at 8 weeks and the rabbits were divided among four groups (n ¼ 6) based on the number of weeks the right knees were remobilized: 0, 8, 16, or 32. Three rabbits (six knees) that did not have operations provided normal control joint capsules. The mRNA levels for collagen types I, II, and III, and MMP-1 and -13 were significantly increased in the joint capsules of the contracture knees in all groups when compared to normal and contralateral limb joint capsules. In contrast, the mRNA levels for TIMP-1, -2, and -3 were decreased in the joint capsules of the contracture knees in all groups when compared to normal and contralateral limb joint capsules. The mRNA levels for lumican and decorin were increased in the joint capsules of the contracture knees in all groups when compared to normal capsules. Many of the changes observed in this animal model are similar to those observed in human joint capsules from posttraumatic elbow contractures, supporting the value of this rabbit model. ß

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Joint capsule matrix turnover in a rabbit model of chronic joint contractures: Correlation with human contractures

Hildebrand

Zhang

Hart

2006

Journal Orthopaedic Research

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“…38 This latter study also reported a decrease in ␣-smooth muscle actin expression in the presence of the MMP inhibitor. This blockade of contraction is difficult to dovetail with the reported side effects of some of these MMP inhibitors in clinical trials in which Duputyren's-like contracture and frozen shoulder were observed [13][14][15] ; however, this may reflect the fact that culture models of collagen lattice contraction only represent a single facet of a more complex disease process. Again, drawing on the analogy with liver fibrosis, a treatment that downregulates TIMPs but increases the activity of MMPs may be an appropriate therapy for DD.…”

Section: Discussionmentioning

confidence: 99%

“…The clinical presentation, when reported in detail, is described as frozen shoulder or a condition resembling DD. 15 Both of these conditions involve similar fibrotic mechanisms (of the shoulder joint capsule in the case of frozen shoulder), the laying down of a collagen-rich ECM, and the involvement of myofibroblast-mediated contraction. 16,17 Although DD and frozen shoulder have different natural histories (the former a progressive disease, the latter usually self-limiting and resolving in time), they may well share common pathways leading to contracture.…”

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confidence: 99%

A Complete Expression Profile of Matrix-Degrading Metalloproteinases in Dupuytren’s Disease

Johnston

Chojnowski

Davidson

et al. 2007

The Journal of Hand Surgery

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Purpose: Dupuytren's disease (DD) is a common fibrotic condition of the palmar fascia, leading to deposition of collagen-rich cords and finger contractions. The metzincin superfamily contains key enzymes in the turnover of collagen and other extracellular matrix macromolecules. A number of broad-spectrum matrix metalloproteinase inhibitors, used in cancer clinical trials, caused side effects of DD-like contractures. We tested the hypothesis that changes in the expression of specific metalloproteinases underlie or contribute to the fibrosis and contracture seen in DD. Methods: We collected tissue from patients with DD and used normal palmar fascia as a control. We profiled the expression of the entire matrix metalloproteinase (MMP), tissue inhibitor of metalloproteinases (TIMP), and a disintegrin and metalloproteinase domain with thrombospondin motif (ADAMTS) gene families in these tissues using real-time reversetranscription polymerase chain reaction. Results: A number of metalloproteinases and inhibitors are regulated in DD. The expression of 3 key collagenases, MMP1, MMP13, and MMP14 is increased significantly in the DD nodule, as is the expression of the collagen biosynthetic enzyme ADAMTS14. The expression of MMP7, an enzyme with broad substrate specificity, is increased in the DD nodule and remains equally expressed in the DD cord. TIMP1 expression is increased significantly in DD nodule compared with normal palmar fascia. Conclusions: This study measured the expression of all MMP, ADAMTS, and TIMP genes in DD. Contraction and fibrosis may result from: (1) increased collagen biosynthesis mediated by increased ADAMTS-14; (2) an increased level of TIMP-1 blocking MMP-1-and MMP-13-mediated collagenolysis; and (3) contraction enabled by MMP-14 -mediated pericellular collagenolysis (and potentially MMP-7), which may escape inhibition by TIMP-1. The complete expression profile will provide a knowledge-based approach to novel therapeutics targeting these genes. (J Hand Surg 2007;32A:343-351.

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“…However, significant side effects from the use of MMP inhibitors have also been documented (Wojtowicz-Praga et al, 1998;Hutchinson et al, 1998;Primrose et al, 1999). Given that the b6-ERK2 interaction mediates MMP-9 secretion and that de novo expression of b6 occurs in epithelial cancer cells, inhibition of MMP activity by targetting either b6 or the ERK2 binding site may offer greater therapeutic specificity in cancer treatment than MMP inhibitors and avoid unwanted side effects.…”

Section: Discussionmentioning

confidence: 99%

Integrin αvβ6-associated ERK2 mediates MMP-9 secretion in colon cancer cells

Dorahy

et al. 2002

Br J Cancer

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There is general consensus that matrix metalloproteinases are involved in tumour progression. We show herein that inhibition of integrin avb6 expression in colon cancer cells suppresses MMP-9 secretion. This integrin-mediated event is dependent upon direct binding between the b6 integrin subunit and extracellular signal-regulated kinase 2. Targetting either b6 or its interaction with extracellular signal-regulated kinase in order to inhibit matrix metalloproteinase activity may offer a useful therapeutic approach in preventing growth and spread of colon cancer.

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Dupuytren's disease and frozen shoulder induced by treatment with a matrix metalloproteinase inhibitor

Cited by 158 publications

References 0 publications

Joint capsule matrix turnover in a rabbit model of chronic joint contractures: Correlation with human contractures

Joint capsule matrix turnover in a rabbit model of chronic joint contractures: Correlation with human contractures

A Complete Expression Profile of Matrix-Degrading Metalloproteinases in Dupuytren’s Disease

Integrin αvβ6-associated ERK2 mediates MMP-9 secretion in colon cancer cells

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