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.
Similar content being viewed by others
References
Al-Qattan MM (2006) Factors in the pathogenesis of Dupuytren’s contracture. J Hand Surg 31A:1527–1534
Augoff K, Ratajczak K, Gosk J, Tabola R, Rutowski R (2006) Gelatinase A activity in Dupuytren’s disease. J Hand Surg 31A:1635–1639
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, Hurst LC (1999) The biochemistry of Dupuytren’s disease. Hand Clin 15:35–42
Badalamente MA, Hurst LC (2000) Enzyme injection as non-surgical treatment of Dupuytren’s disease. J Hand Surg (Am) 25:629–636
Badalamente MA, Hurst LC (2007) Efficacy and safety of injectable mixed collagenases subtypes in the treatment of Dupuytren’s contracture. J Hand Surg (Am) 32:767–774
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 27:1014–1020
Brenner P (2002) Dupuytren’s disease of ring and little finger. Orthop Traumatol 10:138–158
Brew K, Dinakarpandian D, Nagase H (2002) Tissue inhibitors of metalloproteinases: evolution, structure and function. Biochim Biophys Acta 1477:267
Brinckerhoff CE, Matrisian LM (2002) Matrix metalloproteinases: a tail of a frog that became a prince. Nat Rev Mol Cell Biol 3:207–214
Burge P, Hoy G, Regan P, Milne R (1997) Smoking, alcohol and the risk of Dupuytren’s contracture. J Bone Joint Surg (Br) 79:206–210
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
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 17:1762–1764
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)
Hurst LC, Badalamente MA (1999) Nonoperative treatment of Dupuytren’s disease. Hand Clinics 15:97–107
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:907–908
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 322:809–814
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) 32:343–351
Kloen P (1999) New insights in the development of Dupuytren’s contracture: a review. Br J Plast Surg 52:629–635
Luck JV (1959) Dupuytren’s contracture: a new concept of the pathogenesis correlated with surgical management. J Bone Joint Surg (Am) 41:635–664
Massova I, Kotra LP, Fridman R, Mobashery S (1998) Matrix metalloproteinases: structures, evolution, and diversification. FASEB J. 12:1075–1095
Mott JD, Werb Z (2004) Regulation of matrix biology by matrix metalloproteinases. Curr Opin Cell Biol 16:558–564
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 110:187–193
Murrell GAC, Francis MJO, Bromley L (1991) The collagen changes of Dupuytren’s contracture. J Hand Surg (Br) 16:263–266
Nagase H, Woessner JF (1999) Matrix metalloproteinases. J Biol Chem 274:21491–21494
Nagase H, Visse R, Murphy G (2006) Structure and function of matrix metalloproteinases and TIMPs. Cardiovasc Res 69:562–573
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 50:618–622
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 503:158–162
Qian A, Meals RA, Rajfer J, Gonzalez-Cadavid NF (2004) Comparison of gene expression profiles between Peyronie’s disease and Dupuytren’s contracture. Urology 64:399–404
Ramadori G, Knittel T, Saile B (1998) Fibrosis and altered matrix synthesis. Digestion 59:372–375
Ravanti L, Kahari VM (2000) Matrix metalloproteonases in wound repair. Int J Mol Med 6:391–407
Rayan GM (2007) Dupuytren disease: anatomy, pathology, presentation, and treatment. J Bone Joint Surg (Am) 89:189–198
Reynolds JJ (1996) Collagenases and tissue inhibitors of metalloproteinases: a functional balance in tissue degradation. Oral Dis 2:70–76
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 1:10
Shaw RB, Chong AKS, Zhang A, Hentz VR, Chang J (2007) Dupuytren’s disease: history, diagnosis, and treatment. Plast Reconstr Surg 120:44e–54e
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 5:195–203
Smith SP, Devaraj VS, Bunker TD (2001) The association between frozen shoulder and Dupuytren’s disease. J Shoulder Elbow Surg 10:149–151
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) 21:490–495
Swartz WM, Lalonde DH (2008) MOC-PSSM CME Article: Dupuytren’s disease. Plast Reconstr Surg 121:1–10
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
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 112:1279–1286
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 111:1423–1431
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 114:229–236
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 101:280–285
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 98:2739–2745
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)
Visse R, Nagase H (2003) Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry. Circ Res 92:827–839
Vu TH, Werb Z (2000) Matrix metalloproteinases: effectors of development and normal physiology. Genes Dev 14:2123–2133
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ulrich, D., Ulrich, F., Piatkowski, A. et al. Expression of matrix metalloproteinases and their inhibitors in cords and nodules of patients with Dupuytren’s disease. Arch Orthop Trauma Surg 129, 1453–1459 (2009). https://doi.org/10.1007/s00402-008-0726-3
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00402-008-0726-3