The Relationships Among Spatiotemporal Gene Expression, Histology, and Biomechanics Following Full-Length Injury in the Murine Patellar Tendon

University of Cincinnati, Cincinnati, OH, USA.
Journal of Orthopaedic Research (Impact Factor: 2.97). 06/2011; 30(1):28-36. DOI: 10.1002/jor.21484
Source: PubMed

ABSTRACT Tendon injuries are major orthopedic problems that worsen as the population ages. Type-I (Col1) and type-II (Col2) collagens play important roles in tendon midsubstance and tendon-to-bone insertion healing, respectively. Using double transgenic mice, this study aims to spatiotemporally monitor Col1 and Col2 gene expression, histology, and biomechanics up to 8 weeks following a full-length patellar tendon injury. Gene expression and histology were analyzed weekly for up to 5 weeks while mechanical properties were measured at 1, 2, 5, and 8 weeks. At week 1, the healing region displayed loose granulation tissue with little Col1 expression. Col1 expression peaked at 2 weeks, but the ECM was highly disorganized and hypercellular. By 3 weeks, Col1 expression had reduced and by 5 weeks, the ECM was generally aligned along the tendon axis. Col2 expression was not seen in the healing midsubstance or insertion at any time point. The biomechanics of the healing tissue was inadequate at all time points, achieving ultimate loads and stiffnesses of 48% and 63% of normal values by 8 weeks. Future studies will further characterize the cells within the healing midsubstance and insertion using tenogenic markers and compare these results to those of tendon cells during normal development.

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Available from: Jason Shearn, Jul 31, 2015
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    • "These cells migrate to the wound site then express Scx as the tenascin-rich provisional matrix transitions to a collagenous matrix. While direct correlations with biomechanical properties have yet to be made, increased Scx expression during remodeling appears to be commensurate with increased biomechanical properties (Dyment et al., 2011; Scott et al., 2011). Scx expression is necessary, but certainly not sufficient, for the formation of mechanically functional tendon. "
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    • "The curves represent the average of 10 specimens; error bars indicate SEM. Dyment et al., 2012). This finding, coupled with the fact that crosssectional area increased significantly in the injured tendons, indicates that failed healing is not the result of a lack of new tissue formation, but instead is due to the inability of the healing soft tissue to reintegrate with bone. "
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    • "Phase 3: Between 1995 and 2003, our work moved to the tissue/cell level, as we and our collaborators continued to record in vivo tissue forces [32] [33] [34] [35] [36] [37] [38] and initiated studies to identify novel therapies in tissue engineering and functional tissue engineering (FTE) [39] [40] [41] [42] [43] [44] [45] [46] [47] [48] [49]. Phase 4: Our most recent work, between 2004 and 2012, has progressed even smaller to the tissue/cell/molecular levels as we have sought to develop not only design criteria for tissue-engineered tendon and ligament repairs compared to normal tissues [50–74] but also new research directions in " fundamental tissue engineering " at the interface of FTE and developmental biology [75] [76] [77] [78] [79] [80] [81] [82]. What follows are brief summaries of the four phases of our musculoskeletal research. "
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