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. CONCLUSION: 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.

A biomechanical analysis of prophylactic fixation for pathological fractures of the distal third of the humerus.

Twenty-four matched pairs of fresh-frozen humeri from human cadavera were divided randomly into four groups, in order to determine the most biomechanically desirable construct for the prophylactic fixation of impending fractures of the distal third of the humerus. Group I comprised intact humeri and matched humeri in which a 50 per cent lateral, semicylindrical cortical defect of the distal third had been created, resulting in a reproducible model of an impending fracture due to a lytic defect involving 50 per cent cortical disruption at the distal end of the humeral medullary canal. In Group II, such a lateral defect was created in both the right and the left, matched humeri. Group III was composed of humeri in which the defect had been fixed prophylactically with a single plate and the contralateral humeri, which had been treated with double-plating. Group IV comprised specimens in which the defect had been fixed with double-plating as well as those fixed with Rush rods. The fixation of each specimen in Groups III and IV was supplemented with bone cement. Each specimen was tested in torsion to failure, and the resulting peak torque, torsional stiffness, and total energy absorbed were analyzed for each group. The Group-I specimens that had a defect had a significantly lower (p < 0.05) peak torque, torsional stiffness, and total energy absorbed than the intact specimens; all of the specimens with a defect failed at the defect, and all of the intact specimens failed proximally. In Group II, there was a high side-to-side association with respect to peak torque, torsional stiffness, and total energy absorbed.(ABSTRACT TRUNCATED AT 250 WORDS)