Protective effect of exogenous chondroitin 4,6-sulfate in the acute degradation of articular cartilage in the rabbit.
The injection of 2.0 mg chymopapain into the adolescent rabbit knee causes severe loss of articular cartilage proteoglycans (PG). Although chondrocytes attempt to restore lost PG, failure to repair ensues. Pure chondroitin 4,6-sulfate (Condrosulf, IBSA Lugano, Switzerland) has been used in clinical studies of human osteoarthritis (OA) as a slow-acting drug for OA (SYSADOA). Using our model of articular cartilage injury, we examined the effects of oral and intramuscular administration of Condrosulf after chymopapain-induced cartilage injury. In this study, animals received an injection of 2.0 mg chymopapain (Chymodiactin, Boots Pharmaceuticals) into the left knee and were sacrificed after 84 days. The contralateral right knee served as a noninjected control. Some animals received oral Condrosulf while others received intramuscular injections of Condrosulf. Serum keratan sulfate (KS) levels were monitored to ensure degradation of the cartilage PG. Those animals not exhibiting at least a 100% increase of serum KS following chymopapain injection were excluded from the study. At sacrifice, cartilage PG contents were markedly reduced in animals receiving an injection of 2.0 mg chymopapain with no further treatment. In contrast, oral administration of Condrosulf beginning 11 days prior to chymopapain injury resulted in significantly higher (P = 0.0036) cartilage PG contents. Intramuscular administration of Condrosulf resulted in higher, but less significantly so (P = 0.0457), cartilage PG contents. These results suggest that daily Condrosulf treatment prior to and continuing after chymopapain injury may have a protective effect on the damaged cartilage, allowing it to continue to re-synthesize matrix PG after the treatment is discontinued.
Uebelhart
D
D
Department of Clinical Neurosciences and Dermatology, University Hospital of Geneva, Switzerland.
Thonar
E J
EJ
Zhang
J
J
Williams
J M
JM
D000284:Administration, Oral; D000818:Animals; D002358:Cartilage, Articular / Q000737:chemistry / Q000187:drug effects*; D002809:Chondroitin Sulfates / Q000008:administration & dosage / Q000494:pharmacology*; D002917:Chymopapain; D007270:Injections, Intra-Articular; D007273:Injections, Intramuscular; D007632:Keratan Sulfate / Q000097:blood; D008297:Male; D011489:Protein Denaturation / Q000187:drug effects; D011509:Proteoglycans / Q000032:analysis; D011817:Rabbits
D011509:Proteoglycans; C096808:chondroitin 4,6-disulfate; D002809:Chondroitin Sulfates; D007632:Keratan Sulfate; D002917:Chymopapain