Expression of collagen and matrix metalloproteinases in ruptured human anterior cruciate ligament: an in situ hybridization study.
The biological basis for failure of the human anterior cruciate ligament to heal after rupture is unknown. Since this failure could be influenced by abnormalities in matrix protein production or degradation, or both, several diverse matrix protein markers were utilized to survey the state of these extracellular proteins in intrinsic anterior cruciate ligament fibroblasts. Matrix gene expression was visualized by in situ hybridization 9 to 365 days after rupture using probes for type-I collagen, collagenase, 72kDa-gelatinase, and tissue inhibitor of metalloproteinase. Remnants of anterior cruciate ligament were biopsied arthroscopically from 20 patients at reconstruction, fixed in 4% paraformaldehyde, and processed with cDNA probes for the aforementioned mRNAs. mRNA expression of type-I collagen was detected in all specimens, was equally distributed throughout the remnants, and remained evident even at 1 year after injury. Neither of the matrix-degrading enzymes nor their inhibitor (tissue inhibitor of metalloproteinase) was expressed at substantial levels at any time point. Collagen expression within the anterior cruciate ligament confirmed the viability of the ligament remnants for as long as 1 year after rupture. The lack of significant expression of the two matrix-degrading metalloproteinases by the fibroblasts is not consistent with an autodegradation of the remaining ruptured ligament tissue, and whether the lack of matrix remodelling may account, at least in part, for the poor healing response of the anterior cruciate ligament remains to be determined. This initial investigation by in situ hybridization techniques provides a descriptive profile of matrix gene expression in the damaged human anterior cruciate ligament.
Spindler
K P
KP
Department of Orthopaedics and Rehabilitation, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Clark
S W
SW
Nanney
L B
LB
Davidson
J M
JM
D000293:Adolescent; D000328:Adult; D016118:Anterior Cruciate Ligament / Q000378:metabolism*; D000070598:Anterior Cruciate Ligament Injuries; D003094:Collagen / Q000235:genetics*; D005109:Extracellular Matrix / Q000201:enzymology*; D015870:Gene Expression; D006801:Humans; D017403:In Situ Hybridization; D008666:Metalloendopeptidases / Q000235:genetics*; D012421:Rupture
D003094:Collagen; D008666:Metalloendopeptidases