Ro 32-3555, an orally active collagenase selective inhibitor, prevents structural damage in the STR/ORT mouse model of osteoarthritis.
OBJECTIVE
To determine the efficacy of a selective inhibitor of collagenases in an animal model of osteoarthritis (OA).


METHODS
Ro 32-3555, an orally active collagenase selective inhibitor, was administered to STR/ORT mice. Microfocal x-ray-generated images of the hind limbs were visually scored for joint space narrowing, osteophyte formation, and calcification of tendons. Histologic sections of the knees were scored for cartilage changes including loss of surface matrix, fibrillation, and eburnation.


RESULTS
Significant inhibition of joint space narrowing and osteophyte formation was achieved in groups of animals treated with 10-50 mg/kg(-1) of Ro 32-3555. These effects were confirmed histologically in the same groups of animals: histologic analysis revealed that Ro 32-3555 protected cartilage from degradative changes.


CONCLUSIONS
Ro 32-3555, a collagenase selective inhibitor, inhibits both the cartilage and bone changes in this mouse model of OA, and thus shows great potential as a treatment of OA in humans.
Brewster
M
M
Roche Discovery Welwyn, Welwyn Garden City, Hertfordshire, UK.
Lewis
E J
EJ
Wilson
K L
KL
Greenham
A K
AK
Bottomley
K M
KM
D000818:Animals; D002358:Cartilage, Articular / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology; D004195:Disease Models, Animal; D007093:Imidazoles / Q000494:pharmacology*; D007719:Knee Joint / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D008807:Mice, Inbred BALB C; D008852:Microradiography; D010003:Osteoarthritis / Q000000981:diagnostic imaging / Q000473:pathology / Q000517:prevention & control*; D011480:Protease Inhibitors / Q000494:pharmacology*
D007093:Imidazoles; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; C106997:Ro 32-3555