Skip to main content
Top
Published in: MUSCULOSKELETAL SURGERY 1/2013

01-06-2013 | Original Article

Metalloproteases and their inhibitors are altered in both torn and intact rotator cuff tendons

Authors: A. Castagna, E. Cesari, A. Gigante, M. Conti, R. Garofalo

Published in: MUSCULOSKELETAL SURGERY | Special Issue 1/2013

Login to get access

Abstract

Background

We evaluated the role of matrix metalloproteases (MMPs) and their inhibitors which are involved in extracellular matrix remodeling and degradation, in the pathogenesis of chronic rotator cuff tears.

Materials and Methods

Tendon samples were harvested from 13 patients who underwent arthroscopic repair of a rotator cuff tear. Supraspinatus biopsy specimens were harvested en bloc from the arthroscopically intact middle portion of the tendon more than 1 cm from the torn edge, from the lateral edge of the tear, and from the superior one third of the macroscopically intact subscapularis tendon used as control. Histological analysis and an evaluation of the activity of specific metalloproteases and the tissue inhibitors of metalloprotease (TIMP-1, TIMP-2) was done blindly by multiplex sandwich ELISA (Search-Light technology) in each specimen

Results

Histological evidence of tendinopathy was present in all patients with a tear of the rotator cuff, and not in the macroscopically intact subscapularis tendon. There was a significant increase in MMP 1, MMP 2, MMP 3 and in TIMP-1, TIMP-2 levels in all specimens examined, including the macroscopically intact portion of the supraspinatus tendon and in the control specimens

Conclusions

The tissue in the ruptured area of the supraspinatus tendon undergoes marked rearrangement at molecular levels. This involves the activity of MMP 1, 2 and 3, and supports the critical role of MMPs in the tendon physiology. Seemingly intact parts of the injured supraspinatus tendon can present tendinopathic features, with altered cellular metabolism
Literature
1.
go back to reference Kastelic J, Galeski A, Baer E (1978) The multicomposite structure of tendon. Connect Tissue Res 6–1:11–23CrossRef Kastelic J, Galeski A, Baer E (1978) The multicomposite structure of tendon. Connect Tissue Res 6–1:11–23CrossRef
2.
go back to reference Goutallier D, Postel JM, Van Driessche S, Voisin MC (2005) Histological lesions of supraspinatus tendons in full thickness tears of the rotator cuff. Rev Chir Orthop Reparatrice Appar Mot 91–2:109–113CrossRef Goutallier D, Postel JM, Van Driessche S, Voisin MC (2005) Histological lesions of supraspinatus tendons in full thickness tears of the rotator cuff. Rev Chir Orthop Reparatrice Appar Mot 91–2:109–113CrossRef
3.
go back to reference Longo UG, Franceschi F, Ruzzini L, Rabitti C, Morini S, Maffulli N, Denaro V (2008) Histopathology of the supraspinatus tendon in rotator cuff tears. Am J Sports Med 36–3:533–538 Longo UG, Franceschi F, Ruzzini L, Rabitti C, Morini S, Maffulli N, Denaro V (2008) Histopathology of the supraspinatus tendon in rotator cuff tears. Am J Sports Med 36–3:533–538
4.
go back to reference Sharma P, Maffulli N (2006) Biology of tendon injury: healing, modeling and remodeling. J Musculoskelet Neuronal Interact 6–2:181–190 Sharma P, Maffulli N (2006) Biology of tendon injury: healing, modeling and remodeling. J Musculoskelet Neuronal Interact 6–2:181–190
5.
go back to reference Sharma P, Maffulli N (2008) Tendinopathy and tendon injury: the future. Disabil Rehabil 30:1733–1745PubMedCrossRef Sharma P, Maffulli N (2008) Tendinopathy and tendon injury: the future. Disabil Rehabil 30:1733–1745PubMedCrossRef
6.
go back to reference Arnoczky SP, Lavagnino M, Egerbacher M, Caballero O, Gardner K (2007) Matrix metalloproteinase inhibitors prevent a decrease in the mechanical properties of stress-deprived tendons: an in vitro experimental study. Am J Sports Med 35–5:763–769CrossRef Arnoczky SP, Lavagnino M, Egerbacher M, Caballero O, Gardner K (2007) Matrix metalloproteinase inhibitors prevent a decrease in the mechanical properties of stress-deprived tendons: an in vitro experimental study. Am J Sports Med 35–5:763–769CrossRef
7.
go back to reference Magra M, Maffulli N (2005) Matrix metalloproteases: a role in overuse tendinopathies. Br J Sports Med 39–11:789–791CrossRef Magra M, Maffulli N (2005) Matrix metalloproteases: a role in overuse tendinopathies. Br J Sports Med 39–11:789–791CrossRef
8.
go back to reference Magra M, Maffulli N (2005) Molecular events in tendinopathy: a role for metalloproteases. Foot Ankle Clin 10–2:267–277CrossRef Magra M, Maffulli N (2005) Molecular events in tendinopathy: a role for metalloproteases. Foot Ankle Clin 10–2:267–277CrossRef
9.
go back to reference Longo UG, Oliva F, Denaro V, Maffulli N (2008) Oxygen species and overuse tendinopathy in athletes. Disabil Rehabil 30:1563–1571PubMedCrossRef Longo UG, Oliva F, Denaro V, Maffulli N (2008) Oxygen species and overuse tendinopathy in athletes. Disabil Rehabil 30:1563–1571PubMedCrossRef
10.
go back to reference Bedi A, Fox AJ, Kovacevic D, Deng XH, Warren RF, Rodeo SA (2010) Doxycycline-mediated inhibition of matrix metalloproteinases improves healing after rotator cuff repair. Am J Sports Med 38:308–317PubMedCrossRef Bedi A, Fox AJ, Kovacevic D, Deng XH, Warren RF, Rodeo SA (2010) Doxycycline-mediated inhibition of matrix metalloproteinases improves healing after rotator cuff repair. Am J Sports Med 38:308–317PubMedCrossRef
11.
go back to reference Dalton S, Cawston TE, Riley GP, Bayley IJ, Hazleman BL (1995) Human shoulder tendon biopsy samples in organ culture produce procollagenase and tissue inhibitor of metalloproteinases. Ann Rheum Dis 54–7:571–577CrossRef Dalton S, Cawston TE, Riley GP, Bayley IJ, Hazleman BL (1995) Human shoulder tendon biopsy samples in organ culture produce procollagenase and tissue inhibitor of metalloproteinases. Ann Rheum Dis 54–7:571–577CrossRef
12.
go back to reference Gardner K, Arnoczky SP, Caballero O, Lavagnino M (2008) The effect of stress-deprivation and cyclic loading on the TIMP/MMP ratio in tendon cells: an in vitro experimental study. Disabil Rehabil 30:1523–1529PubMedCrossRef Gardner K, Arnoczky SP, Caballero O, Lavagnino M (2008) The effect of stress-deprivation and cyclic loading on the TIMP/MMP ratio in tendon cells: an in vitro experimental study. Disabil Rehabil 30:1523–1529PubMedCrossRef
13.
go back to reference Joseph M, Maresh CM, McCarthy MB, Kraemer WJ, Ledgard F, Arciero CL, Anderson JM, Nindl BC, Mazzocca AD (2009) Histological and molecular analysis of the biceps tendon long head post-tenotomy. J Orthop Res 27–10:1379–1385CrossRef Joseph M, Maresh CM, McCarthy MB, Kraemer WJ, Ledgard F, Arciero CL, Anderson JM, Nindl BC, Mazzocca AD (2009) Histological and molecular analysis of the biceps tendon long head post-tenotomy. J Orthop Res 27–10:1379–1385CrossRef
14.
go back to reference Osawa T, Shinozaki T, Takagishi K (2005) Multivariate analysis of biochemical markers in synovial fluid from the shoulder joint for diagnosis of rotator cuff tears. Rheumatol Int 25–6:436–441CrossRef Osawa T, Shinozaki T, Takagishi K (2005) Multivariate analysis of biochemical markers in synovial fluid from the shoulder joint for diagnosis of rotator cuff tears. Rheumatol Int 25–6:436–441CrossRef
15.
go back to reference Tajana MS, Murena L, Valli F, Passi A, Grassi FA (2009) Correlations between biochemical markers in the synovial fluid and severity of rotator cuff disease. Chir Organi Mov 93(Suppl 1):S41–S48PubMed Tajana MS, Murena L, Valli F, Passi A, Grassi FA (2009) Correlations between biochemical markers in the synovial fluid and severity of rotator cuff disease. Chir Organi Mov 93(Suppl 1):S41–S48PubMed
16.
go back to reference Karousou E, Ronga M, Vigetti D, Passi A, Maffulli N (2008) Collagens, proteoglycans, MMP-2, MMP-9 and TIMPs in human achilles tendon rupture. Clin Orthop Relat Res 466–7:1577–1582CrossRef Karousou E, Ronga M, Vigetti D, Passi A, Maffulli N (2008) Collagens, proteoglycans, MMP-2, MMP-9 and TIMPs in human achilles tendon rupture. Clin Orthop Relat Res 466–7:1577–1582CrossRef
17.
go back to reference Lo IK, Marchuk LL, Hollinshead R, Hart DA, Frank CB (2004) Matrix metalloproteinase and tissue inhibitor of matrix metalloproteinase mRNA levels are specifically altered in torn rotator cuff tendons. Am J Sports Med 32–5:1223–1229CrossRef Lo IK, Marchuk LL, Hollinshead R, Hart DA, Frank CB (2004) Matrix metalloproteinase and tissue inhibitor of matrix metalloproteinase mRNA levels are specifically altered in torn rotator cuff tendons. Am J Sports Med 32–5:1223–1229CrossRef
18.
go back to reference Wang F, Murrell GA, Wang MX (2007) Oxidative stress-induced c-Jun N-terminal kinase (JNK) activation in tendon cells upregulates MMP1 mRNA and protein expression. J Orthop Res 25–3:378–389CrossRef Wang F, Murrell GA, Wang MX (2007) Oxidative stress-induced c-Jun N-terminal kinase (JNK) activation in tendon cells upregulates MMP1 mRNA and protein expression. J Orthop Res 25–3:378–389CrossRef
19.
20.
go back to reference Zafar MS, Mahmood A, Maffulli N (2009) Basic science and clinical aspects of achilles tendinopathy. Sports Med Arthrosc 17–3:190–197CrossRef Zafar MS, Mahmood A, Maffulli N (2009) Basic science and clinical aspects of achilles tendinopathy. Sports Med Arthrosc 17–3:190–197CrossRef
21.
go back to reference Choi HR, Kondo S, Hirose K, Ishiguro N, Hasegawa Y, Iwata H (2002) Expression and enzymatic activity of MMP-2 during healing process of the acute supraspinatus tendon tear in rabbits. J Orthop Res 20–5:927–933CrossRef Choi HR, Kondo S, Hirose K, Ishiguro N, Hasegawa Y, Iwata H (2002) Expression and enzymatic activity of MMP-2 during healing process of the acute supraspinatus tendon tear in rabbits. J Orthop Res 20–5:927–933CrossRef
22.
go back to reference Blaine TA, Kim YS, Voloshin I, Chen D, Murakami K, Chang SS, Winchester R, Lee FY, O’Keefe RJ, Bigliani LU (2005) The molecular pathophysiology of subacromial bursitis in rotator cuff disease. J Shoulder Elbow Surg 14–1(Suppl S):84S–89SCrossRef Blaine TA, Kim YS, Voloshin I, Chen D, Murakami K, Chang SS, Winchester R, Lee FY, O’Keefe RJ, Bigliani LU (2005) The molecular pathophysiology of subacromial bursitis in rotator cuff disease. J Shoulder Elbow Surg 14–1(Suppl S):84S–89SCrossRef
23.
go back to reference Gotoh M, Hamada K, Yamakawa H, Tomonaga A, Inoue A, Fukuda H (1997) Significance of granulation tissue in torn supraspinatus insertions: an immunohistochemical study with antibodies against interleukin-1 beta, cathepsin D, and matrix metalloprotease-1. J Orthop Res 15–1:33–39CrossRef Gotoh M, Hamada K, Yamakawa H, Tomonaga A, Inoue A, Fukuda H (1997) Significance of granulation tissue in torn supraspinatus insertions: an immunohistochemical study with antibodies against interleukin-1 beta, cathepsin D, and matrix metalloprotease-1. J Orthop Res 15–1:33–39CrossRef
24.
go back to reference Tillander B, Franzen L, Norlin R (2002) Fibronectin, MMP-1 and histologic changes in rotator cuff disease. J Orthop Res 20–6:1358–1364CrossRef Tillander B, Franzen L, Norlin R (2002) Fibronectin, MMP-1 and histologic changes in rotator cuff disease. J Orthop Res 20–6:1358–1364CrossRef
25.
go back to reference Matthews TJ, Hand GC, Rees JL, Athanasou NA, Carr AJ (2006) Pathology of the torn rotator cuff tendon. Reduction in potential for repair as tear size increases. J Bone Joint Surg Br 88–4:489–495 Matthews TJ, Hand GC, Rees JL, Athanasou NA, Carr AJ (2006) Pathology of the torn rotator cuff tendon. Reduction in potential for repair as tear size increases. J Bone Joint Surg Br 88–4:489–495
26.
go back to reference Kannus P, Jozsa L (1991) Histopathological changes preceding spontaneous rupture of a tendon. A controlled study of 891 patients. J Bone Joint Surg Am 73–10:1507–1525 Kannus P, Jozsa L (1991) Histopathological changes preceding spontaneous rupture of a tendon. A controlled study of 891 patients. J Bone Joint Surg Am 73–10:1507–1525
27.
go back to reference Voloshin I, Gelinas J, Maloney MD, O’Keefe RJ, Bigliani LU, Blaine TA (2005) Proinflammatory cytokines and metalloproteases are expressed in the subacromial bursa in patients with rotator cuff disease. Arthroscopy 21–9:1076 Voloshin I, Gelinas J, Maloney MD, O’Keefe RJ, Bigliani LU, Blaine TA (2005) Proinflammatory cytokines and metalloproteases are expressed in the subacromial bursa in patients with rotator cuff disease. Arthroscopy 21–9:1076
28.
go back to reference Longo UG, Ronga M, Maffulli N (2009) Achilles tendinopathy. Sports Med Arthrosc 17–2:112–126CrossRef Longo UG, Ronga M, Maffulli N (2009) Achilles tendinopathy. Sports Med Arthrosc 17–2:112–126CrossRef
29.
go back to reference Lakemeier S, Braun J (2011) Efe T expression of matrix metalloproteinases 1, 3, and 9 in differing extents of tendon retraction in the torn rotator cuff. Knee Surg Sports Traumatol Arthrosc 19(10):1760–1765PubMedCrossRef Lakemeier S, Braun J (2011) Efe T expression of matrix metalloproteinases 1, 3, and 9 in differing extents of tendon retraction in the torn rotator cuff. Knee Surg Sports Traumatol Arthrosc 19(10):1760–1765PubMedCrossRef
30.
go back to reference Rees JD, Maffulli N, Cook J (2009) Management of tendinopathy. Am J Sports Med 37–9:1855–1867CrossRef Rees JD, Maffulli N, Cook J (2009) Management of tendinopathy. Am J Sports Med 37–9:1855–1867CrossRef
31.
go back to reference Robertson CM, Chen CT, Shindle MK, Cordasco FA, Rodeo SA, Warren RF (2012) Failed healing of rotator cuff repair correlates with altered collagenase and gelatinase in supraspinatus and subscapularis tendons. Am J Sports Med 40(9):1993–2001. doi:10.1177/0363546512456519 PubMedCrossRef Robertson CM, Chen CT, Shindle MK, Cordasco FA, Rodeo SA, Warren RF (2012) Failed healing of rotator cuff repair correlates with altered collagenase and gelatinase in supraspinatus and subscapularis tendons. Am J Sports Med 40(9):1993–2001. doi:10.​1177/​0363546512456519​ PubMedCrossRef
32.
go back to reference Bedi A, Kovacevic D, Hettrich C, Gulotta LV, Ehteshami JR, Warren RF, Rodeo SA (2010) The effect of matrix metalloproteinase inhibition on tendon-to-bone healing in a rotator cuff repair model. J Shoulder Elbow Surg 19:384–391PubMedCrossRef Bedi A, Kovacevic D, Hettrich C, Gulotta LV, Ehteshami JR, Warren RF, Rodeo SA (2010) The effect of matrix metalloproteinase inhibition on tendon-to-bone healing in a rotator cuff repair model. J Shoulder Elbow Surg 19:384–391PubMedCrossRef
Metadata
Title
Metalloproteases and their inhibitors are altered in both torn and intact rotator cuff tendons
Authors
A. Castagna
E. Cesari
A. Gigante
M. Conti
R. Garofalo
Publication date
01-06-2013
Publisher
Springer Milan
Published in
MUSCULOSKELETAL SURGERY / Issue Special Issue 1/2013
Print ISSN: 2035-5106
Electronic ISSN: 2035-5114
DOI
https://doi.org/10.1007/s12306-013-0264-1

Other articles of this Special Issue 1/2013

MUSCULOSKELETAL SURGERY 1/2013 Go to the issue