High levels of expression of collagenase-3 (MMP-13) in pathological conditions associated with a foreign-body reaction.
A foreign-body-type host response can contribute to the induction and release of collagenolytic tissue-destructive enzymes of pathogenetic significance. Our aim was to analyse collagenase-3 in two conditions with putative involvement of foreign-body reactions. Synovial membrane-like tissue samples were obtained from cases of aseptic loosening of a total hip replacement (THR) and osteoarthritis (OA). The reverse transcription polymerase chain reaction (RT-PCR) disclosed that all the samples from patients contained collagenase-3 mRNA compared with only three out of ten control samples. The identity of the RT-PCR amplification product was confirmed by nucleotide sequencing. Immunohistochemical staining showed that collagenase-3 was present in endothelial cells, macrophages and fibroblasts, including those found in the synovial lining. This finding was confirmed by avidin-biotin-peroxidase complex-alkaline phosphatase-anti-alkaline phosphatase double staining and the specificity of the staining by antigen preabsorption using recombinant human collagenase-3. Collagenase-3 was released into the extracellular space and thus found in the synovial fluid in all patient samples as shown by Western blotting. The similar extent of collagenase-3 expression in aseptic loosening and OA compared with the low expression in control synovial membrane suggests involvement of a similar, foreign-body-based pathogenetic component in both. Comparative analysis of collagenase-3 and of foreign particles indicates that paracrine factors rather than phagocytosis per se are responsible for the induction of collagenase-3. We suggest that due to its localisation and substrate specificity, collagenase-3 may play a significant pathogenetic role in accelerating tissue destruction in OA and in aseptic loosening of a THR.
University of Helsinki, Helsinki University Central Hospital and the ORTON Research Institute, Invalid Foundation, Finland.
S
S
Imai
Y T
YT
Konttinen
M
M
Jumppanen
O
O
Lindy
A
A
Ceponis
P
P
Kemppinen
T
T
Sorsa
S
S
Santavirta
J W
JW
Xu
C
C
Lopéz-Otín
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000032:analysis; D019644:Arthroplasty, Replacement, Hip; D017364:Collagenases / Q000032:analysis* / Q000235:genetics; D004396:Coloring Agents; D004730:Endothelium, Vascular / Q000473:pathology; D005110:Extracellular Space / Q000201:enzymology; D005260:Female; D005347:Fibroblasts / Q000473:pathology; D005549:Foreign-Body Reaction / Q000201:enzymology* / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D006621:Hip Joint / Q000201:enzymology; D006622:Hip Prosthesis; D006801:Humans; D008264:Macrophages / Q000473:pathology; D008297:Male; D053509:Matrix Metalloproteinase 13; D008875:Middle Aged; D010003:Osteoarthritis / Q000201:enzymology / Q000235:genetics; D019899:Paracrine Communication; D011475:Prosthesis Failure; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D013379:Substrate Specificity; D013582:Synovial Fluid / Q000201:enzymology; D013583:Synovial Membrane / Q000201:enzymology*
D004396:Coloring Agents; D012333:RNA, Messenger; D000469:Alkaline Phosphatase; D017364:Collagenases; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13