Collagenase 1 and collagenase 3 expression in a guinea pig model of osteoarthritis.
OBJECTIVE
To analyze the in vivo compartmental expression of collagenases 1 and 3 (MMP-1 and MMP-13) in the Hartley guinea pig model of spontaneously occurring osteoarthritis (OA) for the purpose of elucidating their roles in the pathogenesis of OA.


METHODS
Competitive reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry quantification of messenger RNA (mRNA) and protein levels in medial and lateral tibial cartilage obtained from the knee joints of 2-month-old (no OA) and 12-month-old (OA) guinea pigs.


RESULTS
The patterns of mRNA expression of collagenases 1 and 3 varied with the age of the animal and the compartment of the knee. We also found focal areas of collagenase 1 and collagenase 3 proteins localized to the extracellular matrix of OA lesion sites, coincident with three-quarter/one-quarter collagen cleavage. Collagenase 3 protein was also abundant throughout the medial tibial cartilage of 2-month-old animals.


CONCLUSIONS
This represents the first description of bona fide collagenase 1 in a rodent species. Recent evidence, however, based on analysis of mitochondrial DNA homologies, suggests that the guinea pig is not a member of the order Rodentia and may be more closely allied with lagomorphs. This taxonomic controversy leaves open to question the issue of the expression of collagenase 1 in other rodents, such as mice and rats. The presence of active collagenases 1 and 3 at OA lesion sites is consistent with an important role of these enzymes in the cartilage degradation of OA in guinea pigs. The expression of collagenase 3 in medial tibial cartilage from 2-month-old guinea pigs may signify a role of this enzyme in cartilage remodeling with growth and development, or it may represent an early molecular manifestation of OA.
Huebner
J L
JL
Duke University Medical Center, Durham, North Carolina 27710, USA.
Otterness
I G
IG
Freund
E M
EM
Caterson
B
B
Kraus
V B
VB
D000818:Animals; D015139:Blotting, Southern; D017364:Collagenases / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers / Q000737:chemistry; D004195:Disease Models, Animal; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics / Q000378:metabolism; D006168:Guinea Pigs; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020781:Matrix Metalloproteinase 1; D053509:Matrix Metalloproteinase 13; D008592:Menisci, Tibial / Q000201:enzymology / Q000473:pathology; D051379:Mice; D010003:Osteoarthritis / Q000201:enzymology* / Q000209:etiology / Q000473:pathology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013045:Species Specificity
D017931:DNA Primers; D012333:RNA, Messenger; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D017364:Collagenases; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; C507081:Mmp13 protein, mouse; C507083:Mmp13 protein, rat; D020781:Matrix Metalloproteinase 1