Treatment with calcitonin prevents the net loss of collagen, hyaluronan and proteoglycan aggregates from cartilage in the early stages of canine experimental osteoarthritis.
OBJECTIVE
To evaluate the effect of calcitonin (CT) on the histology and biochemistry of articular cartilage from unstable operated and nonoperated knee in a canine model of experimental osteoarthritis (OA).


METHODS
Eighteen dogs underwent anterior cruciate ligament transection (ACLT) of the right knee and were randomly distributed into three groups of six dogs each. From day-1 after surgery until sacrifice 84 days post-ACLT, each dog received a daily nasal spray that delivered the placebo, 100 units of CT or 400 units of CT. Histologic lesions were scored. Hyaluronan (HA) and antigenic keratan sulfate (AgKS) were quantified by enzyme-linked immunosorbent assays (ELISAs), whereas aggrecan molecules extracted under nondissociative conditions were characterized by velocity gradient centrifugation.


RESULTS
All canine cruciate-deficient knees developed OA. At a daily dose of 400 units, CT had no effect on the size of osteophytes but significantly reduced the severity of cartilage histologic lesions in unstable knees. CT also enhanced the HA content as well as the size distribution and relative abundance of fast-sedimenting aggrecan aggregates in cartilage from both operated and nonoperated knees. On the other hand, in the CT-treated group, the cartilage content of AgKS increased in operated joints, but not in nonoperated joints.


CONCLUSIONS
Because CT delivered as a nasal spray markedly reduced the severity of most OA changes, both at the histological and biochemical level, this form of therapy may have benefits for humans who have recently experienced a traumatic knee injury, and as well as for dogs who spontaneously rupture their ACL.
El Hajjaji
Hafida
H
Christian de Duve Institute of Cellular Pathology, Connective Tissue Group, Department of Biochemistry, Catholic University of Louvain in Brussels, 1200 Brussels, Belgium.
Williams
James M
JM
Devogelaer
Jean-Pierre
JP
Lenz
Mary Ellen
ME
Thonar
Eugene J-M A
EJ
Manicourt
Daniel-Henri
DH
D053674:Aggrecans; D000818:Animals; D016118:Anterior Cruciate Ligament / Q000601:surgery; D002116:Calcitonin / Q000627:therapeutic use*; D002358:Cartilage, Articular / Q000378:metabolism*; D002499:Centrifugation, Density Gradient / Q000379:methods; D003094:Collagen / Q000032:analysis*; D004285:Dogs; D016326:Extracellular Matrix Proteins / Q000032:analysis; D006614:Hindlimb; D006820:Hyaluronic Acid / Q000032:analysis*; D007632:Keratan Sulfate / Q000032:analysis; D037181:Lectins, C-Type; D010003:Osteoarthritis / Q000188:drug therapy* / Q000473:pathology; D011509:Proteoglycans / Q000032:analysis*
D053674:Aggrecans; D016326:Extracellular Matrix Proteins; D037181:Lectins, C-Type; D011509:Proteoglycans; D006820:Hyaluronic Acid; D002116:Calcitonin; D003094:Collagen; D007632:Keratan Sulfate