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The mechanical environment in dupuytren's contracture determines cell contractility and associated MMP‐mediated matrix remodeling
Author(s) -
Verhoekx Jennifer S.N.,
Beckett Kate S.,
Bisson Marcus A.,
McGrouther Duncan A.,
Grobbelaar Adriaan O.,
Mudera Vivek
Publication year - 2013
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.22220
Subject(s) - matrix metalloproteinase , contractility , matrix (chemical analysis) , extracellular matrix , microbiology and biotechnology , contraction (grammar) , contracture , chemistry , anatomy , medicine , pathology , biology , surgery , chromatography
Matrix metalloproteinases (MMPs) are expressed in Dupuytren's contracture and play a role in matrix remodeling. We tested the role of tension on contractility and MMP expression in Dupuytren's nodule and cord cells. Cells were subjected to pre‐determined loading patterns of known repeatable magnitudes (static load, unloading, and overloading) and tested for MMP gene expression (MMP‐1, ‐2, ‐9, ‐13, and TIMP‐1, ‐2) and force generation using a tension‐culture force monitor. Matrix remodeling was assessed by addition of cytochalasin D and residual matrix tension was quantified. Nodule compared to cord and control cells demonstrate greater force generation and remodeling ( p < 0.05). Nodule cells subjected to a reduced load and overloading led to threefold increase of MMP‐1, ‐2, and ‐9 compared to static load, whilst cord and control cells only showed a twofold increase of MMP‐9. Nodule cells subjected to overloading showed a twofold increase in TIMP‐2 expression, whilst cord and control cells showed a twofold increase in TIMP‐1 expression. Nodule cells differ from cord cells by increased force generation in response to changes in the mechanical environment and related MMP/TIMP‐mediated matrix remodeling. In turn this may lead to permanent matrix shortening and digital contracture. Interventional therapies should be aimed at nodule cells to prevent contraction and subsequent permanent matrix remodeling. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 328–334, 2013