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Published in: Archives of Orthopaedic and Trauma Surgery 11/2009

01-11-2009 | Orthopaedic Surgery

Expression of matrix metalloproteinases and their inhibitors in cords and nodules of patients with Dupuytren’s disease

Authors: Dietmar Ulrich, Franziska Ulrich, Andrzej Piatkowski, Norbert Pallua

Published in: Archives of Orthopaedic and Trauma Surgery | Issue 11/2009

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Abstract

Introduction

Dupuytren’s disease is a fibroproliferative disorder characterized by thickening of the palmar fascia. Several studies indicate that MMPs and TIMPs may play a key role in the onset or progression of Dupuytren’s disease and related disorders. In this study, we used a quantitative reverse-transcription PCR methodology to profile the expression of TIMP1, TIMP2, MMP2, and MMP9 in nodule and cord tissue from patients with Dupuytren’s disease and compared this with normal palmar fascia taken at carpal tunnel release.

Materials and methods

Tissue from patients with Dupuytren’s disease was taken at fasciectomy (n = 30; 23 men and 7 women; average age 61.3 ± 9.5 years). Samples were divided into regions of nodule and cord according to gross morphology. Normal fascia was taken from patients without Dupuytren’s contracture who had carpal tunnel release (n = 30; 14 men and 16 women; average age 63 ± 11 years). Expression of mRNA was calculated using a relative quantification method (Pfaffl). Statistical analysis was performed using the Mann–Whitney test. The level of significance was considered to be P < 0.05.

Results

In comparison to normal fascia, the cords and nodules from patients with Dupuytren’s disease showed significant upregulation for TIMP1 and TIMP2 (P < 0.05). The expression of TIMP1 was significantly higher in nodules in comparison to cord tissue (P < 0.05). The expression of MMP2 was significantly upregulated in tissue of patients with Dupuytren’s contracture in comparison to normal tissue (P < 0.05). The expression of MMP2 was significantly higher in nodules in comparison to cord tissue (P < 0.05). There was no significant difference in the relative expression of MMP9 in nodules and cord tissue of patients with Dupuytren’s contracture in comparison to normal fascia from patients with carpal tunnel syndrome.

Conclusions

The balance between MMPs and their natural inhibitors is disturbed in patients with Dupuytren’s disease. The decrease in MMP-to-TIMP expression can cause increased synthesis and deposition of collagen, leading to palmar fibromatosis. The high expression of MMP2 may represent an unsuccessful attempt to reduce collagen deposition. In the future, a treatment that downregulates TIMPs but increases the activity of MMPs may be an appropriate therapy for Dupuytren’s disease.
Literature
1.
go back to reference Al-Qattan MM (2006) Factors in the pathogenesis of Dupuytren’s contracture. J Hand Surg 31A:1527–1534 Al-Qattan MM (2006) Factors in the pathogenesis of Dupuytren’s contracture. J Hand Surg 31A:1527–1534
2.
go back to reference Augoff K, Ratajczak K, Gosk J, Tabola R, Rutowski R (2006) Gelatinase A activity in Dupuytren’s disease. J Hand Surg 31A:1635–1639 Augoff K, Ratajczak K, Gosk J, Tabola R, Rutowski R (2006) Gelatinase A activity in Dupuytren’s disease. J Hand Surg 31A:1635–1639
3.
go back to reference Badalamente MA, Sampson SP, Hurst LC, Dowd A, Miyasaka K (1996) The role of transforming growth factor beta in Dupuytren’s disease. J Hand Surg 21A:210–215 Badalamente MA, Sampson SP, Hurst LC, Dowd A, Miyasaka K (1996) The role of transforming growth factor beta in Dupuytren’s disease. J Hand Surg 21A:210–215
4.
go back to reference Badalamente MA, Hurst LC (1999) The biochemistry of Dupuytren’s disease. Hand Clin 15:35–42PubMed Badalamente MA, Hurst LC (1999) The biochemistry of Dupuytren’s disease. Hand Clin 15:35–42PubMed
5.
go back to reference Badalamente MA, Hurst LC (2000) Enzyme injection as non-surgical treatment of Dupuytren’s disease. J Hand Surg (Am) 25:629–636CrossRef Badalamente MA, Hurst LC (2000) Enzyme injection as non-surgical treatment of Dupuytren’s disease. J Hand Surg (Am) 25:629–636CrossRef
6.
go back to reference Badalamente MA, Hurst LC (2007) Efficacy and safety of injectable mixed collagenases subtypes in the treatment of Dupuytren’s contracture. J Hand Surg (Am) 32:767–774CrossRef Badalamente MA, Hurst LC (2007) Efficacy and safety of injectable mixed collagenases subtypes in the treatment of Dupuytren’s contracture. J Hand Surg (Am) 32:767–774CrossRef
7.
go back to reference Berndt A, Kosmehl H, Mandel U et al (1995) TGF beta and bFGF synthesis and localization in Dupuytren’s disease (nodular palmar fibromatosis) relative to cellular activity, myofibroblast phenotype and oncofetal variants of fibronectin. Histochem J 27:1014–1020PubMed Berndt A, Kosmehl H, Mandel U et al (1995) TGF beta and bFGF synthesis and localization in Dupuytren’s disease (nodular palmar fibromatosis) relative to cellular activity, myofibroblast phenotype and oncofetal variants of fibronectin. Histochem J 27:1014–1020PubMed
8.
go back to reference Brenner P (2002) Dupuytren’s disease of ring and little finger. Orthop Traumatol 10:138–158CrossRef Brenner P (2002) Dupuytren’s disease of ring and little finger. Orthop Traumatol 10:138–158CrossRef
9.
go back to reference Brew K, Dinakarpandian D, Nagase H (2002) Tissue inhibitors of metalloproteinases: evolution, structure and function. Biochim Biophys Acta 1477:267 Brew K, Dinakarpandian D, Nagase H (2002) Tissue inhibitors of metalloproteinases: evolution, structure and function. Biochim Biophys Acta 1477:267
10.
go back to reference Brinckerhoff CE, Matrisian LM (2002) Matrix metalloproteinases: a tail of a frog that became a prince. Nat Rev Mol Cell Biol 3:207–214PubMedCrossRef Brinckerhoff CE, Matrisian LM (2002) Matrix metalloproteinases: a tail of a frog that became a prince. Nat Rev Mol Cell Biol 3:207–214PubMedCrossRef
11.
go back to reference Burge P, Hoy G, Regan P, Milne R (1997) Smoking, alcohol and the risk of Dupuytren’s contracture. J Bone Joint Surg (Br) 79:206–210CrossRef Burge P, Hoy G, Regan P, Milne R (1997) Smoking, alcohol and the risk of Dupuytren’s contracture. J Bone Joint Surg (Br) 79:206–210CrossRef
12.
go back to reference Cordova A, Tripoli M, Corradino B, Napoli P, Moschella F (2005) Dupuytren’s contracture: an update of biomolecular aspects and therapeutic perspectives. J Hand Surg (Br) 30(6):557–562 Cordova A, Tripoli M, Corradino B, Napoli P, Moschella F (2005) Dupuytren’s contracture: an update of biomolecular aspects and therapeutic perspectives. J Hand Surg (Br) 30(6):557–562
13.
go back to reference Forbes JM, Thallas V, Tomas MC et al (2003) The breakdown of preexisting advanced glycation end products is associated with reduced renal fibrosis in experimental diabetes. FASEB J 17:1762–1764PubMed Forbes JM, Thallas V, Tomas MC et al (2003) The breakdown of preexisting advanced glycation end products is associated with reduced renal fibrosis in experimental diabetes. FASEB J 17:1762–1764PubMed
14.
go back to reference Hoegemann A, Wolfhard U, Kendoff D, Board TN, Olivier LC (2008) Results of total aponeurectomy for Dupuytren’s contracture in 61 patients. A retrospective clinical study. Arch Orthop Trauma Surg, 31 May (Epub ahead of print) Hoegemann A, Wolfhard U, Kendoff D, Board TN, Olivier LC (2008) Results of total aponeurectomy for Dupuytren’s contracture in 61 patients. A retrospective clinical study. Arch Orthop Trauma Surg, 31 May (Epub ahead of print)
15.
go back to reference Hurst LC, Badalamente MA (1999) Nonoperative treatment of Dupuytren’s disease. Hand Clinics 15:97–107PubMed Hurst LC, Badalamente MA (1999) Nonoperative treatment of Dupuytren’s disease. Hand Clinics 15:97–107PubMed
16.
go back to reference Hutchinson JW, Tierney GM, Parsons SL, Davis TR (1998) Dupuytren’s disease and frozen shoulder induced by treatment with a matrix metalloproteinase inhibitor. J Bone Joint Surg 80B:907–908CrossRef Hutchinson JW, Tierney GM, Parsons SL, Davis TR (1998) Dupuytren’s disease and frozen shoulder induced by treatment with a matrix metalloproteinase inhibitor. J Bone Joint Surg 80B:907–908CrossRef
17.
go back to reference Imai K, Hiramatsu A, Fukushima D, Pierschabacher D, Okada Y (1997) Degradation of decorin by matrix metalloproteinases: identification of the cleavage sites, kinetic analyses and transforming growth factor-β1 release. Biochem J 322:809–814PubMed Imai K, Hiramatsu A, Fukushima D, Pierschabacher D, Okada Y (1997) Degradation of decorin by matrix metalloproteinases: identification of the cleavage sites, kinetic analyses and transforming growth factor-β1 release. Biochem J 322:809–814PubMed
18.
go back to reference Johnston P, Chojnowski AJ, Davidson RK et al (2007) A complete expression profile of matrix-degrading metalloproteinases in Dupuytren’s disease. J Hand Surg (Am) 32:343–351CrossRef Johnston P, Chojnowski AJ, Davidson RK et al (2007) A complete expression profile of matrix-degrading metalloproteinases in Dupuytren’s disease. J Hand Surg (Am) 32:343–351CrossRef
19.
go back to reference Kloen P (1999) New insights in the development of Dupuytren’s contracture: a review. Br J Plast Surg 52:629–635PubMedCrossRef Kloen P (1999) New insights in the development of Dupuytren’s contracture: a review. Br J Plast Surg 52:629–635PubMedCrossRef
20.
go back to reference Luck JV (1959) Dupuytren’s contracture: a new concept of the pathogenesis correlated with surgical management. J Bone Joint Surg (Am) 41:635–664 Luck JV (1959) Dupuytren’s contracture: a new concept of the pathogenesis correlated with surgical management. J Bone Joint Surg (Am) 41:635–664
21.
go back to reference Massova I, Kotra LP, Fridman R, Mobashery S (1998) Matrix metalloproteinases: structures, evolution, and diversification. FASEB J. 12:1075–1095PubMed Massova I, Kotra LP, Fridman R, Mobashery S (1998) Matrix metalloproteinases: structures, evolution, and diversification. FASEB J. 12:1075–1095PubMed
22.
go back to reference Mott JD, Werb Z (2004) Regulation of matrix biology by matrix metalloproteinases. Curr Opin Cell Biol 16:558–564PubMedCrossRef Mott JD, Werb Z (2004) Regulation of matrix biology by matrix metalloproteinases. Curr Opin Cell Biol 16:558–564PubMedCrossRef
23.
go back to reference Moyer KE, Banducci DR, Graham WP 3rd, Ehrlich HP (2002) Dupuytren’s disease: physiologic changes in nodule and cord fibroblasts through aging in vitro. Plast Reconstr Surg 110:187–193PubMedCrossRef Moyer KE, Banducci DR, Graham WP 3rd, Ehrlich HP (2002) Dupuytren’s disease: physiologic changes in nodule and cord fibroblasts through aging in vitro. Plast Reconstr Surg 110:187–193PubMedCrossRef
24.
go back to reference Murrell GAC, Francis MJO, Bromley L (1991) The collagen changes of Dupuytren’s contracture. J Hand Surg (Br) 16:263–266 Murrell GAC, Francis MJO, Bromley L (1991) The collagen changes of Dupuytren’s contracture. J Hand Surg (Br) 16:263–266
26.
go back to reference Nagase H, Visse R, Murphy G (2006) Structure and function of matrix metalloproteinases and TIMPs. Cardiovasc Res 69:562–573PubMedCrossRef Nagase H, Visse R, Murphy G (2006) Structure and function of matrix metalloproteinases and TIMPs. Cardiovasc Res 69:562–573PubMedCrossRef
27.
go back to reference Pan D, Watson HK, Swigart C, Thomson JG, Honig SC, Narayan D (2003) Microarray gene analysis and expression profiles of Dupuytren’s contracture. Ann Plast Surg 50:618–622PubMedCrossRef Pan D, Watson HK, Swigart C, Thomson JG, Honig SC, Narayan D (2003) Microarray gene analysis and expression profiles of Dupuytren’s contracture. Ann Plast Surg 50:618–622PubMedCrossRef
28.
go back to reference Patterson ML, Atkinson SJ, Knäuper V, Murphy G (2003) Specific collagenolysis by gelatinase A, MMP-2, is determined by the hemopexin domain and not the fibronectin-like domain. FEBS Lett 503:158–162CrossRef Patterson ML, Atkinson SJ, Knäuper V, Murphy G (2003) Specific collagenolysis by gelatinase A, MMP-2, is determined by the hemopexin domain and not the fibronectin-like domain. FEBS Lett 503:158–162CrossRef
29.
go back to reference Qian A, Meals RA, Rajfer J, Gonzalez-Cadavid NF (2004) Comparison of gene expression profiles between Peyronie’s disease and Dupuytren’s contracture. Urology 64:399–404PubMedCrossRef Qian A, Meals RA, Rajfer J, Gonzalez-Cadavid NF (2004) Comparison of gene expression profiles between Peyronie’s disease and Dupuytren’s contracture. Urology 64:399–404PubMedCrossRef
30.
go back to reference Ramadori G, Knittel T, Saile B (1998) Fibrosis and altered matrix synthesis. Digestion 59:372–375PubMedCrossRef Ramadori G, Knittel T, Saile B (1998) Fibrosis and altered matrix synthesis. Digestion 59:372–375PubMedCrossRef
31.
go back to reference Ravanti L, Kahari VM (2000) Matrix metalloproteonases in wound repair. Int J Mol Med 6:391–407PubMed Ravanti L, Kahari VM (2000) Matrix metalloproteonases in wound repair. Int J Mol Med 6:391–407PubMed
32.
go back to reference Rayan GM (2007) Dupuytren disease: anatomy, pathology, presentation, and treatment. J Bone Joint Surg (Am) 89:189–198 Rayan GM (2007) Dupuytren disease: anatomy, pathology, presentation, and treatment. J Bone Joint Surg (Am) 89:189–198
33.
go back to reference Reynolds JJ (1996) Collagenases and tissue inhibitors of metalloproteinases: a functional balance in tissue degradation. Oral Dis 2:70–76PubMed Reynolds JJ (1996) Collagenases and tissue inhibitors of metalloproteinases: a functional balance in tissue degradation. Oral Dis 2:70–76PubMed
34.
go back to reference Satish L, LaFramboise WA, O’Gorman DB et al (2008) Identification of differentially expressed genes in fibroblasts derived from patients with Dupuytren’s contracture. BMC Med Genomics 1:10PubMedCrossRef Satish L, LaFramboise WA, O’Gorman DB et al (2008) Identification of differentially expressed genes in fibroblasts derived from patients with Dupuytren’s contracture. BMC Med Genomics 1:10PubMedCrossRef
35.
go back to reference Shaw RB, Chong AKS, Zhang A, Hentz VR, Chang J (2007) Dupuytren’s disease: history, diagnosis, and treatment. Plast Reconstr Surg 120:44e–54ePubMedCrossRef Shaw RB, Chong AKS, Zhang A, Hentz VR, Chang J (2007) Dupuytren’s disease: history, diagnosis, and treatment. Plast Reconstr Surg 120:44e–54ePubMedCrossRef
36.
go back to reference Smeets R, Ulrich D, Unglaub F, Wöltje M, Pallua N (2008) Effect of regenerated cellulose/collagen matrix on proteases in wound exudate of patients with chronic venous ulceration. Int Wound J 5:195–203PubMedCrossRef Smeets R, Ulrich D, Unglaub F, Wöltje M, Pallua N (2008) Effect of regenerated cellulose/collagen matrix on proteases in wound exudate of patients with chronic venous ulceration. Int Wound J 5:195–203PubMedCrossRef
37.
go back to reference Smith SP, Devaraj VS, Bunker TD (2001) The association between frozen shoulder and Dupuytren’s disease. J Shoulder Elbow Surg 10:149–151PubMedCrossRef Smith SP, Devaraj VS, Bunker TD (2001) The association between frozen shoulder and Dupuytren’s disease. J Shoulder Elbow Surg 10:149–151PubMedCrossRef
38.
go back to reference Starkweather KD, Lattuga S, Hurst LC et al (1996) Collagenase in the treatment of Dupuytren’s disease: an in vitro study. J Hand Surg (Am) 21:490–495CrossRef Starkweather KD, Lattuga S, Hurst LC et al (1996) Collagenase in the treatment of Dupuytren’s disease: an in vitro study. J Hand Surg (Am) 21:490–495CrossRef
39.
go back to reference Swartz WM, Lalonde DH (2008) MOC-PSSM CME Article: Dupuytren’s disease. Plast Reconstr Surg 121:1–10PubMedCrossRef Swartz WM, Lalonde DH (2008) MOC-PSSM CME Article: Dupuytren’s disease. Plast Reconstr Surg 121:1–10PubMedCrossRef
40.
go back to reference Tarlton JF, Meagher P, Brown RA, McGrouther DA, Bailey AJ, Afoke A (1998) Mechanical stress in vitro induces increased expression of MMPs 2 and 9 in excised Dupuytren’s disease tissue. J Hand Surg 23B:297–302 Tarlton JF, Meagher P, Brown RA, McGrouther DA, Bailey AJ, Afoke A (1998) Mechanical stress in vitro induces increased expression of MMPs 2 and 9 in excised Dupuytren’s disease tissue. J Hand Surg 23B:297–302
41.
go back to reference Ulrich D, Hrynyschyn K, Pallua N (2003) Matrix metalloproteinases and tissue inhibitors of metalloproteinase in sera and tissue of patients with Dupuytren’s disease. Plast Reconstr Surg 112:1279–1286PubMedCrossRef Ulrich D, Hrynyschyn K, Pallua N (2003) Matrix metalloproteinases and tissue inhibitors of metalloproteinase in sera and tissue of patients with Dupuytren’s disease. Plast Reconstr Surg 112:1279–1286PubMedCrossRef
42.
go back to reference Ulrich D, Noah EM, von Heimburg D, Pallua N (2003) TIMP-1, MMP-2, MMP-9, and PIIINP as serum markers for skin fibrosis in patients following severe burn trauma. Plast Reconstr Surg 111:1423–1431PubMedCrossRef Ulrich D, Noah EM, von Heimburg D, Pallua N (2003) TIMP-1, MMP-2, MMP-9, and PIIINP as serum markers for skin fibrosis in patients following severe burn trauma. Plast Reconstr Surg 111:1423–1431PubMedCrossRef
43.
go back to reference Ulrich D, Lichtenegger F, Eblenkamp M, Repper D, Pallua N (2004) Matrix metalloproteinases, tissue inhibitors of metalloproteinases, aminoterminal propeptide of procollagen type III, and hyaluronan in sera and tissue of patients with capsular contracture after augmentation with TRILUCENT breast implants. Plast Reconstr Surg 114:229–236PubMedCrossRef Ulrich D, Lichtenegger F, Eblenkamp M, Repper D, Pallua N (2004) Matrix metalloproteinases, tissue inhibitors of metalloproteinases, aminoterminal propeptide of procollagen type III, and hyaluronan in sera and tissue of patients with capsular contracture after augmentation with TRILUCENT breast implants. Plast Reconstr Surg 114:229–236PubMedCrossRef
44.
go back to reference Unemori EN, Beck LS, Lee WP et al (1993) Human relaxin decreases collagen accumulation in vivo in two rodent models of fibrosis. J Invest Dermatol 101:280–285PubMedCrossRef Unemori EN, Beck LS, Lee WP et al (1993) Human relaxin decreases collagen accumulation in vivo in two rodent models of fibrosis. J Invest Dermatol 101:280–285PubMedCrossRef
45.
go back to reference Unemori EN, Pickford LB, Al Salles et al (1996) Relaxin induces an extracellular matrix-degrading phenotype in human lung fibroblasts in vitro and inhibits lung fibrosis in a murine model in vivo. J Clin Invest 98:2739–2745PubMedCrossRef Unemori EN, Pickford LB, Al Salles et al (1996) Relaxin induces an extracellular matrix-degrading phenotype in human lung fibroblasts in vitro and inhibits lung fibrosis in a murine model in vivo. J Clin Invest 98:2739–2745PubMedCrossRef
46.
go back to reference Unglaub F, Loos B, Schwarz S, Kneser U, Dragu A, Horch RE (2008) Phlegmonous-infection in first degree Dupuytren’s disease. Arch Orthop Trauma Surg, 20 March (Epub ehead of print) Unglaub F, Loos B, Schwarz S, Kneser U, Dragu A, Horch RE (2008) Phlegmonous-infection in first degree Dupuytren’s disease. Arch Orthop Trauma Surg, 20 March (Epub ehead of print)
47.
go back to reference Visse R, Nagase H (2003) Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry. Circ Res 92:827–839PubMedCrossRef Visse R, Nagase H (2003) Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry. Circ Res 92:827–839PubMedCrossRef
48.
go back to reference Vu TH, Werb Z (2000) Matrix metalloproteinases: effectors of development and normal physiology. Genes Dev 14:2123–2133PubMedCrossRef Vu TH, Werb Z (2000) Matrix metalloproteinases: effectors of development and normal physiology. Genes Dev 14:2123–2133PubMedCrossRef
Metadata
Title
Expression of matrix metalloproteinases and their inhibitors in cords and nodules of patients with Dupuytren’s disease
Authors
Dietmar Ulrich
Franziska Ulrich
Andrzej Piatkowski
Norbert Pallua
Publication date
01-11-2009
Publisher
Springer-Verlag
Published in
Archives of Orthopaedic and Trauma Surgery / Issue 11/2009
Print ISSN: 0936-8051
Electronic ISSN: 1434-3916
DOI
https://doi.org/10.1007/s00402-008-0726-3

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