Metalloproteases and rotator cuff disease

Buono, Angelo Del; Oliva, Francesco; Longo, Umile Giuseppe; Rodeo, Scott A.; Orchard, John; Denaro, Vincenzo; Maffulli, Nicola

doi:10.1016/j.jse.2011.10.020

Cited by 99 publications

(87 citation statements)

References 116 publications

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“…1,2 Collagenases or matrix metalloproteinases (MMPs) have been shown to play an important role in the enzymatic matrix degradation cascade associated with tendon injury and disease. [3][4][5][6] Tendon degeneration is an active, cell-mediated process that may result from a failure to regulate specific MMP activities in response to repeated injury or mechanical strain. After tendon rupture, increased activity of MMPs and increased matrix turnover have been associated with further deterioration in the quality of the collagen network.…”

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confidence: 99%

Enhancement of Achilles tendon repair mediated by matrix metalloproteinase inhibition via systemic administration of doxycycline

Kessler

Barr

Greenwald

et al. 2013

Journal Orthopaedic Research

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Collagenases or matrix metalloproteinases (MMPs) have been shown to play an important role in the matrix degradation cascade associated with Achilles tendon rupture and disease. The goal of this study was to examine the effects of daily administration of doxycycline (Doxy) through oral gavage on MMP activity and on the repair quality of Achilles tendons in vivo. Our findings indicate that Achilles tendon transection resulted in increasing MMP-8 activity from 2 to 6 weeks post-injury, with peak increases in activity occurring at 4 weeks post-injury. Doxy adiministration at clinically relevant serum concentrations was found to significantly inhibit MMP activity after continuous treatment for 4 weeks, but not for continuous administration for shorter durations (96 h or 2 weeks). Extended doxy administration was also associated with improved collagen fibril organization, and enhanced biomechanical properties (stiffness, ultimate tensile strength, maximum load to failure, and elastic toughness). Our findings indicate that a temporal delay exists between Achilles tendon transection and associated increases in MMP-8 activity in situ. Our findings suggest that inhibition of MMP-8 at its peak activity levels ameliorates fibrosis development and improves biomechanical properties of the Achilles tendon. Keywords: achilles tendon; matrix metalloproteinase; doxycycline; tendon rupture and repair Achilles tendon tears are devastating injuries, and have unpredictable outcomes with respect to return to function.1,2 Collagenases or matrix metalloproteinases (MMPs) have been shown to play an important role in the enzymatic matrix degradation cascade associated with tendon injury and disease.3-6 Tendon degeneration is an active, cell-mediated process that may result from a failure to regulate specific MMP activities in response to repeated injury or mechanical strain. After tendon rupture, increased activity of MMPs and increased matrix turnover have been associated with further deterioration in the quality of the collagen network.7-13 Downregulation of tissue inhibitors of MMPs (TIMPS) is also associated with disregulation of the ratio of MMP to TIMP activity, and has been implicated in the pathogenesis of tendinopathy. [8][9][10][11][12][13][14][15][16] Tenocyte production of MMP-1 and -3 underscores the potential for non-lymphocyte mediated cytokine production of proteases inducing local matrix changes. 17 Tetracyclines, through a mechanism independent of their antibiotic effects, have been shown to substantially inhibit the action of MMPs, such as collagenase.18-21 Specifically, doxycycline (doxy) is considered to be the most potent tetracycline MMP inhibitor, whose activity is mediated both by direct and indirect mechanisms of action, and has been applied therapeutically in a variety of clinical applications.18-21 The use of doxy in tendon repair had been previously explored in vivo, though contradictory findings regarding its efficacy have been reported. [22][23][24] Consequently, MMP inhibitors and their activity ...

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confidence: 99%

Enhancement of Achilles tendon repair mediated by matrix metalloproteinase inhibition via systemic administration of doxycycline

Kessler

Barr

Greenwald

et al. 2013

Journal Orthopaedic Research

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“…Nevertheless, we are not yet able to define how, in vivo, the ESWT acts on exposed tissues. They may provide mechanical and biological stimuli determining the activation of a complex network of molecules, including a large panel of cytokines and metalloproteinases 24,[35][36][37] .…”

Section: Resultsmentioning

confidence: 99%

Experimental studies on the biological effects of extracorporeal shock wave therapy on tendon models. A review of the literature

Visco

Vulpiani

Torrisi

et al. 2014

MLTJ

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SummaryEncouraging results using extracorporeal shock wave therapy (ESWT) for treating chronic tendinopathies were recently obtained, although the specific mechanisms by which it induces therapeutic effects remain largely unknown. In order to provide possible explications of such clinical efficacy, several reports have investigated the effects of ESWT on animal models and different kind of cultured cells. Our contribute in establishing the potential outcome of ESWT on human primary cultured tenocytes, derived from healthy compared to ruptured tendons, have supported the growing evidence that shock waves may supply faster post-injury recovery. The purpose of this review was to summarize and evaluate the available basic scientific evidences for using ESWT in tendon pathologies, suggesting possible shock waves-induced mechanisms of tissue repair.

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“…In rabbit models of medial collateral ligament (MCL) tear, the administration of platelet-derived growth factor (PDGF)-BB significantly improved the biomechanical properties of the femur-MCLtibia complex [13]. Growth factors exert different functions and are involved in inflammation, angiogenesis, wound and soft tissue healing [14,15]. PRP is the novel and emerging approach to management of tendon, ligament and cartilage disorders [15].…”

Section: Discussionmentioning

confidence: 99%

Microfractures at the rotator cuff footprint: a randomised controlled study

Osti

Buono

Maffulli

2013

International Orthopaedics (SICOT)

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Purpose Microfractures at the footprint may be a potential additional source of growth factor and enhance the tendon healing at the bone-tendon junction when repairing rotator cuff tears. Methods Fifty-seven patients who underwent shoulder arthroscopy for repair of complete rotator cuff tears were randomly divided into two groups, using a block randomisation procedure. Patients underwent microfracture at the footprint in the treatment group. The patients in the control group (n=29) did not receive that treatment. All patients had the same post-operative rehabilitation protocol. Results The two groups were homogeneous. There was a significant improvement from baseline to the last minimum follow-up of two years. At three months from the index procedure, visual analogue scale (VAS), range of motion (ROM) and University of California at Los Angeles (UCLA) and Constant scores were significantly better in group 1 than in group 2 (P<.05). At the last follow-up (minimum two years), clinical and functional outcomes were further improved in both the groups but inter-group differences were not significant. No technique-related complications were recorded. Conclusions Microfractures at the footprint are simple, safe, inexpensive and effective at producing less pain in the short term in patients who undergo rotator cuff repair, but at two years they do not result in significantly different outcomes, either clinically or at imaging, compared to traditional rotator cuff repair.

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Metalloproteases and rotator cuff disease

Cited by 99 publications

References 116 publications

Enhancement of Achilles tendon repair mediated by matrix metalloproteinase inhibition via systemic administration of doxycycline

Enhancement of Achilles tendon repair mediated by matrix metalloproteinase inhibition via systemic administration of doxycycline

Experimental studies on the biological effects of extracorporeal shock wave therapy on tendon models. A review of the literature

Microfractures at the rotator cuff footprint: a randomised controlled study

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