Amelioration of lapine osteoarthritis by treatment with glycosaminoglycan-peptide association complex (Rumalon).
The chondroprotective potential of glycosaminoglycan-peptide association complex (GP-C) was examined in the medial meniscectomy model of lapine osteoarthritis (OA). Prophylactic treatment with increasing doses of intramuscular GP-C (0.05-0.5 ml/kg) caused a significant reduction in OA lesion area and histologic scores, and the effect on disease activity appeared to be dose related. The DNA and uronic acid contents of OA tissue were unaffected by prophylactic treatment with GP-C. However, levels of hydroxyproline in OA cartilage increased to near control levels with prophylactic treatment. Cartilage levels of active and total metalloproteinases that digest proteoglycans were elevated in rabbits with OA; prophylactic treatment with low-dose GP-C (0.05 ml/kg) produced a significant reduction in active, but not total, enzyme. Cartilage levels of tissue inhibitor of metalloproteinases in animals with OA were comparable with control levels, but rose with increasing doses of GP-C. We also investigated GP-C as a therapeutic treatment in animals that had already developed OA lesions. Carbon black retention and histologic score returned to near-normal after therapeutic treatment with GP-C. Uronic acid and hydroxyproline levels were decreased in OA cartilage. Therapeutic treatment with GP-C had no statistically significant effect on uronic acid levels, but was associated with increased hydroxyproline content in the cartilage. The changes in metalloproteinase and metalloproteinase inhibitor were similar to those found in the studies of prophylactic treatment. The findings in this animal model may help explain some of the beneficial effects of GP-C in human OA.
Dean
D D
DD
Veterans Administration Medical Center, Research Service, Miami, FL 33125.
Muniz
O E
OE
Rodriquez
I
I
Carreno
M R
MR
Morales
S
S
Agundez
A
A
Madan
M E
ME
Altman
R D
RD
Annefeld
M
M
Howell
D S
DS
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use*; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004247:DNA / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D006909:Hydroxyproline / Q000378:metabolism; D007273:Injections, Intramuscular; D008666:Metalloendopeptidases / Q000378:metabolism; D010003:Osteoarthritis / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control; D011817:Rabbits; D014020:Tissue Extracts / Q000008:administration & dosage / Q000627:therapeutic use*; D019714:Tissue Inhibitor of Metalloproteinases; D014574:Uronic Acids / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D006023:Glycoproteins; D014020:Tissue Extracts; D019714:Tissue Inhibitor of Metalloproteinases; D014574:Uronic Acids; C000562:Rumalon; D004247:DNA; D008666:Metalloendopeptidases; D006909:Hydroxyproline