Injury-induced changes in mRNA levels differ widely between anterior cruciate ligament and medial collateral ligament.
BACKGROUND
The drastic difference in healing capacity between the anterior cruciate ligament and the medial collateral ligament is still largely unexplained. Few studies have compared the profiles of messenger ribonucleic acid expression for healing-associated molecules in ligaments during the course of healing.


OBJECTIVE
Injury responses of the injured anterior cruciate ligament and medial collateral ligament are characterized by very different profiles of angiogenesis-promoting and repair-associated gene expression during the healing process.


METHODS
Controlled laboratory study.


METHODS
Reverse-transcriptase polymerase chain reaction was used to assay expression of messenger ribonucleic acid for 11 healing- and angiogenesis-associated molecules at 3 days and 2, 6, and 16 weeks after anterior cruciate ligament or medial collateral ligament injury in adult female New Zealand White rabbits.


RESULTS
Marked differences were found in the postinjury changes in messenger ribonucleic acid levels in the anterior cruciate ligament compared to the medial collateral ligament. Notably, messenger ribonucleic acid levels for the important repair-associated growth factor transforming growth factor-beta1 did not increase in injured anterior cruciate ligament at any time point. Similarly, unlike the injured medial collateral ligament, no statistically significant increases in messenger ribonucleic acid levels for the important scar matrix protein collagen III were detected in injured anterior cruciate ligament. In contrast, matrix metalloproteinase messenger ribonucleic acid levels were markedly elevated in injured anterior cruciate ligament but only modestly increased in medial collateral ligament.


CONCLUSIONS
The results suggest that injury leads to an antifibrotic, catabolic response in the rabbit anterior cruciate ligament, possibly to prevent fibrosis and diminish the risk for loss of joint motion.


CONCLUSIONS
The development of effective biologically based treatments for anterior cruciate ligament injuries will need to incorporate strategies to deal with the significant differences in the molecular responses to injury of these tissues.
Beye
Jasmine A
JA
McCaig Institute for Bone and Joint Health, Calgary, Alberta, Canada.
Hart
David A
DA
Bray
Robert C
RC
McDougall
Jason J
JJ
Salo
Paul T
PT
D000818:Animals; D016118:Anterior Cruciate Ligament / Q000098:blood supply / Q000503:physiopathology*; D000070598:Anterior Cruciate Ligament Injuries; D024042:Collagen Type I / Q000235:genetics; D024061:Collagen Type III / Q000235:genetics; D005260:Female; D008233:Lymphotoxin-alpha / Q000235:genetics; D053505:Matrix Metalloproteinases, Secreted / Q000235:genetics; D017888:Medial Collateral Ligament, Knee / Q000098:blood supply / Q000293:injuries* / Q000503:physiopathology*; D018919:Neovascularization, Physiologic / Q000235:genetics*; D020932:Nerve Growth Factor / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics*; D011817:Rabbits; D019700:Thrombospondin 1 / Q000235:genetics; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D014945:Wound Healing / Q000235:genetics*
D024042:Collagen Type I; D024061:Collagen Type III; D008233:Lymphotoxin-alpha; D012333:RNA, Messenger; D019700:Thrombospondin 1; D019714:Tissue Inhibitor of Metalloproteinases; D042461:Vascular Endothelial Growth Factor A; D020932:Nerve Growth Factor; D014568:Urokinase-Type Plasminogen Activator; D053505:Matrix Metalloproteinases, Secreted