We have found that internal tendon cells live within a pericellular ECM that is between the cells and the load-bearing fibrillar type I collagen. Further, we have demonstrated that MMPs 2 and 9 are expressed in vivo after injury. Similarly, We have established that in vitro, tendon cells increase the production of MMP-2, MMP-9 and MMP-14 after attachment to type I collagen. Our overall hypothesis is: after injury, tendon cells proliferate and migrate and in so doing disrupt their previous steady-state ECM contacts and form new ECM interactions which include type I collagen. This change in ECM ligands, and our preliminary work suggests type I collagen ligation may be key, is part of the constellation of cues that result in the induction of wound healing proteins. As tendon healing then progresses, MMPs play an integral role in catabolic remodeling, growth factor modulation and new matrix deposition. To evaluate this general model of tendon healing, we propose the following in vivo and in vitro approaches: 1. expand our experimental manipulation of tendon cells in vitro to study the mechanisms by which ECM influences the expression of these genes. 2. examine in vivo the functional role of MMP-9 and MMP-14 in tendon repair by the evaluation of tendon healing in null mice. 3. carry out a survey of gene expression as a first step to understanding the greater context within which the collagen-elicited MMP response occurs.
| Boregowda, Rajeev K; Krovic, Brooke M; Ritty, Timothy M (2012) Selective integrin subunit reduction disrupts fibronectin extracellular matrix deposition and fibrillin 1 gene expression. Mol Cell Biochem 369:205-16 |
