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This Article Full Text Full Text (PDF) All Versions of this Article: 293/4/R1552    most recent 00423.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Martinez, D. A. Articles by Grindeland, R. E. Search for Related Content PubMed PubMed Citation Articles by Martinez, D. A. Articles by Grindeland, R. E.

INFLAMMATION AND CYTOKINES

Temporal extracellular matrix adaptations in ligament during wound healing and hindlimb unloading

¹Connective Tissue Physiology Laboratory, Department of Health and Human Performance, and ²Biomedical Engineering Program, Department of Mechanical Engineering, University of Houston, Houston, Texas; ³Office of the President, Idaho State University Administration Building, Pocatello, Idaho; ⁴Orthopedics Research Laboratory, Department of Orthopedics and Rehabilitation and Department of Biomedical Engineering, University of Wisconsin, Madison, Wisconsin; and ⁵Life Sciences Research Division, National Aeronautics and Space Administration-Ames Research Center, Moffett Field, California

Submitted 15 June 2007 ; accepted in final form 9 August 2007

Previous data from spaceflight studies indicate that injured muscle and bone heal slowly and abnormally compared with ground controls, strongly suggesting that ligaments or tendons may not repair optimally as well. Thus the objective of this study was to investigate the biochemical and molecular gene expression of the collagen extracellular matrix in response to medial collateral ligament (MCL) injury repair in hindlimb unloaded (HLU) rodents. Male rats were assigned to 3- and 7-wk treatment groups with three subgroups each: sham control, ambulatory healing (Amb-healing), and HLU-healing groups. Amb- and HLU-healing animals underwent bilateral surgical transection of their MCLs, whereas control animals were subjected to sham surgeries. All surgeries were performed under isoflurane anesthesia. After 3 wk or 7 wk of HLU, rats were euthanized and MCLs were surgically isolated and prepared for molecular or biochemical analyses. Hydroxyproline concentration and hydroxylysylpyridinoline collagen cross-link contents were measured by HPLC and showed a substantial decrement in surgical groups. MCL tissue cellularity, quantified by DNA content, remained significantly elevated in all HLU-healing groups vs. Amb-healing groups. MCL gene expression of collagen type I, collagen type III, collagen type V, fibronectin, decorin, biglycan, lysyl oxidase, matrix metalloproteinase-2, and tissue inhibitor of matrix metalloproteinase-1, measured by real-time quantitative PCR, demonstrated differential expression in the HLU-healing groups compared with Amb-healing groups at both the 3- and 7-wk time points. Together, these data suggest that HLU affects dense fibrous connective tissue wound healing and confirms previous morphological and biomechanical data that HLU inhibits the ligament repair processes.

collagen; cross-links; hindlimb suspension; real-time quantitative PCR; rat

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