title: Changes in gene expression of individual matrix metalloproteinases differ in response to mechanical unloading of tendon fascicles in explant culture.
abstract: Immobilization of the tendon and ligament has been shown to result in a rapid and significant decrease in material properties. It has been proposed that tissue degradation leading to tendon rupture or pain in humans may also be linked to mechanical unloading following focal tendon injury. Hence, understanding the remodeling mechanism associated with mechanical unloading has relevance for the human conditions of immobilization (e.g., casting), delayed repair of tendon ruptures, and potentially overuse injuries as well. This is the first study to investigate the time course of gene expression changes associated with tissue harvest and mechanical unloading culture in an explant model. Rat tail tendon fascicles were harvested and placed in culture unloaded for up to 48 h and then evaluated using qRT-PCR for changes in two anabolic and four catabolic genes at 12 time points. Our data demonstrates that Type I Collagen, Decorin, Cathepsin K, and MMP2 gene expression are relatively insensitive to unloaded culture conditions. However, changes in both MMP3 and MMP13 gene expression are rapid, dramatic, sustained, and changing during at least the first 48 h of unloaded culture. This data will help to further elucidate the mechanism for the loss of mechanical properties associated with mechanical unloading in tendon.
authors.affiliation: Department of Biomedical Engineering, Orthopaedic Research Center, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA.
authors.forename: Diane R
authors.initials: DR
authors.lastname: Leigh
authors.forename: Eduardo L
authors.initials: EL
authors.lastname: Abreu
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Derwin
mesh_terms: D000818:Animals; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D058575:Decorin; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000235:genetics* / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000235:genetics* / Q000378:metabolism; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013314:Stress, Mechanical; D013710:Tendons / Q000201:enzymology* / Q000502:physiology; D016474:Weight-Bearing
chemical_list: D024042:Collagen Type I; C546878:DCN protein, human; C546880:Dcn protein, rat; D058575:Decorin; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans; D012333:RNA, Messenger; D053509:Matrix Metalloproteinase 13; C507083:Mmp13 protein, rat; D019278:Matrix Metalloproteinase 3