title: Isolated fibrillar damage in tendons stimulates local collagenase mRNA expression and protein synthesis.
abstract: The etiology of repetitive stress injuries in tendons has not been clearly identified. While minor trauma has been implicated as an inciting factor, the precise magnitude and structural level of tissue injury that initiates this degenerative cascade has not been determined. The purpose of this study was to determine if isolated tendon fibril damage could initiate an upregulation of interstitial collagenase (MMP13) mRNA and protein in tendon cells associated with the injured fibril(s). Rat tail tendon fascicles were subjected to in vitro tensile loading until isolated fibrillar damage was documented. Once fibrillar damage occurred, the tendons were immediately unloaded to 100g and maintained at that displacement for 24h under tissue culture conditions. In addition, non-injured tendon fascicles were maintained under unloaded (stress-deprived) conditions in culture for 24h to act as positive controls. In situ hybridization or immunohistochemistry was then performed to localize collagenase mRNA expression or protein synthesis, respectively. Fibrillar damage occurred at a similar stress (41.13+/-5.94MPa) and strain (13.24+/-1.94%) in the experimental tendons. In situ hybridization and immunohistochemistry demonstrated an upregulation of interstitial collagenase mRNA and protein, respectively, in only those cells associated with the damaged fibril(s). In the control (stress-deprived) specimens, collagenase mRNA expression and protein synthesis were observed throughout the fascicle. The results suggest that isolated fibrillar damage and the resultant upregulation of collagenase mRNA and protein in this damaged area occurs through a mechanobiological understimulation of tendon cells. This collagenase production may weaken the tendon and put more of the extracellular matrix at risk for further damage during subsequent loading.
authors.affiliation: Laboratory for Comparative Orthopaedic Research, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Lavagnino
authors.forename: Steven P
authors.initials: SP
authors.lastname: Arnoczky
authors.forename: Monika
authors.initials: M
authors.lastname: Egerbacher
authors.forename: Keri L
authors.initials: KL
authors.lastname: Gardner
authors.forename: Meghan E
authors.initials: ME
authors.lastname: Burns
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation; D053509:Matrix Metalloproteinase 13 / Q000096:biosynthesis* / Q000235:genetics*; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013708:Tendon Injuries / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology
chemical_list: D012333:RNA, Messenger; D053509:Matrix Metalloproteinase 13