Do Matrix Metalloproteases and Tissue Inhibitors of Metalloproteases in Tenocytes of the Rotator Cuff Differ with Varying Donor Characteristics?

Franka Klatte-Schulz,Christian Gerhardt,Stephan Pauly,Sven Geißler,Britt Wildemann,Thomas Aleyt,Markus Scheibel

doi:10.3390/ijms160613141

Abstract

An imbalance between matrix metalloproteases (MMPs) and the tissue inhibitors of metalloproteases (TIMPs) may have a negative impact on the healing of rotator cuff tears. The aim of the project was to assess a possible relationship between clinical and radiographic characteristics of patients such as the age, sex, as well as the degenerative status of the tendon and the MMPs and TIMPs in their tenocyte-like cells (TLCs). TLCs were isolated from ruptured supraspinatus tendons and quantitative Real-Time PCR and ELISA was performed to analyze the expression and secretion of MMPs and TIMPs. In the present study, MMPs, mostly gelatinases and collagenases such as MMP-2, -9 and -13 showed an increased expression and protein secretion in TLCs of donors with higher age or degenerative status of the tendon. Furthermore, the expression and secretion of TIMP-1, -2 and -3 was enhanced with age, muscle fatty infiltration and tear size. The interaction between MMPs and TIMPs is a complex process, since TIMPs are not only inhibitors, but also activators of MMPs. This study shows that MMPs and TIMPs might play an important role in degenerative tendon pathologies.

Highlights

Matrix metalloproteases (MMPs) are a large family of proteolytic enzymes, which can degrade all components of the extracellular tendon matrix [1,2]
The aim of the project was to examine the expression and secretion of matrix metalloproteases (MMPs) and tissue inhibitors of metalloproteases (TIMPs) in tenocyte-like cells (TLCs) of Supraspinatus (SSP) tendon tears from donors differing in their degenerative status, age and sex
The analysis revealed an age-dependent increase in the mRNA-expression levels of MMP-2, -9, -13 and TIMP-2, -3 (Figure 3A)

Summary

Introduction

Matrix metalloproteases (MMPs) are a large family of proteolytic enzymes, which can degrade all components of the extracellular tendon matrix [1,2]. Their activities are antagonized by the interaction with the tissue inhibitors of metalloproteases (TIMPs). The balance between MMPs and TIMPs plays a critical role in tendon degeneration and healing [3,4]. Reconstruction is associated with high failure rates [5,6,7], mainly linked to the formation of inferior, disorganized scar tissue at the tendon bone insertion site [8,9]. The mechanisms underlying the poor tendon healing are widely unknown. Since the MMPs and TIMPs regulate tendon modeling and remodeling, it is hypothesized that the development of tendon pathologies is dependent on the MMP/TIMP balance [2,10]

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Conclusion