Effects of diacerhein in an accelerated canine model of osteoarthritis.
OBJECTIVE
To determine whether diacerhein has a disease-modifying effect in an accelerated canine model of osteoarthritis.


METHODS
Fourteen adult mongrel dogs underwent unilateral L4-S1 dorsal root ganglionectomy (DRG), followed 3 weeks later by ipsilateral anterior cruciate ligament transection. Seven dogs received diacerhein (15-20 mg/kg) daily throughout the interval between DRG and sacrifice, eight weeks after ligament transection. The other seven dogs served as OA controls.


RESULTS
The mean volume of synovial fluid obtained from the OA knee of the diacerhein-treated dogs was approximately 40% less than that from the OA knee of the controls. In addition, diacerhein appeared to reduce the severity of fibrillation (femoral condyle) and full-thickness ulceration (trochlear ridge) of the articular cartilage and the level of collagenase activity in extracts of the OA cartilage, and to increase net PG synthesis in the OA cartilage, although none of the above changes were statistically significant.


CONCLUSIONS
The differences between the diacerhein group and untreated OA controls, even though not statistically significant, suggest that diacerhein was active in this rapidly progressive model of OA. Because changes associated with initiation of OA may be different than those associated with progression, whether diacerhein has a disease-modifying effect should be examined in a less rapidly progressive model.
Brandt
K D
KD
Rheumatology Division, Indiana University School of Medicine, Indianapolis 46202-5103, USA.
Smith
G
G
Kang
S Y
SY
Myers
S
S
O'Connor
B
B
Albrecht
M
M
D000818:Animals; D000070598:Anterior Cruciate Ligament Injuries; D000880:Anthraquinones / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D002357:Cartilage Diseases / Q000517:prevention & control; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology; D017364:Collagenases / Q000378:metabolism; D004195:Disease Models, Animal; D004285:Dogs; D005122:Exudates and Transudates / Q000166:cytology; D007719:Knee Joint / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008666:Metalloendopeptidases / Q000378:metabolism; D010003:Osteoarthritis / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D011509:Proteoglycans / Q000096:biosynthesis; D013582:Synovial Fluid / Q000166:cytology; D013583:Synovial Membrane / Q000473:pathology; D014456:Ulcer / Q000517:prevention & control
D000880:Anthraquinones; D000894:Anti-Inflammatory Agents, Non-Steroidal; D011509:Proteoglycans; C025292:diacerein; D017364:Collagenases; D008666:Metalloendopeptidases