Mature & Aging Tendons: Extracellular Matrix Interactions in the Injury Response
Small leucine-rich proteoglycans (SLRPs) are extracellular matrix molecules that are important in the fundamental processes of growth, aging, and repair. The expression and accumulation of two SLRPs common in tendon, decorin and biglycan, differ dramatically during these processes. For example, in the immediate response to tendon injury, expression of these SLRPs recapitulates that seen during development, i.e., high biglycan expression initially with a dramatic decrease during remodeling while decorin initially increases and remains relatively constant. Given that the developmental sequence is thought to be a model for improved healing in tendon and other soft tissues, further understanding of the roles of these SLRPs in healing tendon is of value. The overall objective of this study is to determine the coordinate regulatory role(s) of decorin and biglycan in the re-establishment of structure and function during the repair response to injury in mature tendons and to define the effects of aging on decorin/biglycan mediated regulation of tendon repair.
To satisfy this objective, we will use knockout mice, employing a patellar tendon injury model previously developed in our lab. Briefly, a plastic-coated backing is placed beneath the tendon to offer support (1). A 0.75 mm biopsy punch is used to create a full thickness partial transection of the tendon (2). Removal of the backing leaves a distinct and reproducible injury (3). Healing will be assessed through biomechanical testing as well as other biological and organizational assays at various post-injury time points.
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In addition, we are performing experiments aimed at distinguishing the regulatory effects of decorin and biglycan during tendon development and healing from their "static" role in mature tissue. In particular, by enzymatically digesting proteoglycans in fully-formed mouse tendons, we can remove the "static" effects of these molecules. Comparing across digested tendons from wild type, decorin knockout and biglycan knockout mice then allows us then to isolate and discern the developmental role of SLRPs.
This study is designed to help explain the mechanical and structural results so as to begin to elucidate potential mechanisms responsible for the differential roles of decorin and biglycan with maturation and aging. This information will allow further investigation into the contrasting and potentially compensatory roles of these SLRPs that may aid in design of improved treatment modalities for tendon injuries.
For more information see:
Huang TF, Robinson PS, Kazam E, Iozzo RV, Soslowsky LJ: Elastic and viscoelastic mechanical properties of patellar tendons from decorin and biglycan knockout mice, Trans Orthop Res Soc 29:854, 2004.
Lin TW, Cardenas L, Glaser DL, Soslowsky LJ: Utilizing knockout mice to investigate the roles of interleukins 4 and 6 in tendon healing, Trans Orthop Res Soc 29: 266, 2004.
Robinson PS, Huang TF, Kazam E, Iozzo RV, Birk DE, Soslowsky LJ: Influence of Decorin and Biglycan on Mechanical Properties of Multiple Tendons in Knockout Mice, J Biomech Eng 127(1):181-5, 2005.
Lin TW, Cardenas L, Glaser DL, Soslowsky LJ: Tendon healing in interleukin-4 and interleukin-6 knockout mice, J Biomech 39(1):61-9, 2006.
Beason DP, Zgonis MH, Ansorge HL, Birk DE, Soslowsky LJ: Healing in a Mouse Patellar Tendon Injury Model: Effect of Age, Trans Orthop Res Soc 32:885, 2007.