The protective effect of OP-1 on articular cartilage in the development of osteoarthritis.
OBJECTIVE
The purpose of this study was to determine whether osteogenic protein 1 (OP-1) would protect articular cartilage from degeneration during the development of osteoarthritis (OA) in the rabbit anterior cruciate ligament transection (ACLT) model. Previous studies have shown that OP-1 is vital to cartilage matrix integrity and repair, stimulates synthesis of cartilage matrix components, proteoglycans, and collagen, and has a protective effect against catabolic mediators like matrix metalloproteinases and interleukin-1.


METHODS
The rabbit ACLT model was used in which the anterior cruciate ligament was transected leading to OA. OP-1 was delivered to the joint surgically for approximately 6 weeks by implantation of an Alzet osmotic pump into the medial thigh with a catheter threaded from the pump into the knee joint. Forty rabbits (20 control and 20 experimental) had the ACLT surgery and implantation of the pump performed simultaneously. They were sacrificed after 9 weeks for analysis. The OA was graded using the Outerbridge classification with India Ink staining. Histological staining and histomorphometry with Hematoxylin & Eosin and Safranin O were performed to analyze OA progression and semi-quantitative polymerase chain reaction (PCR) was performed for anabolic and catabolic genes.


RESULTS
The experimental group had an average Outerbridge score of 1.8 vs 2.5 for the controls (P<0.05). Histomorphometry showed 10.9% surface deterioration or an average depression of 0.05mm vs 22.3% and 0.1mm for the controls (P<0.05). Semi-quantitative PCR showed a significantly greater expression of aggrecan and collagen type II in the OP-1 treated cartilage when compared to controls and less expression of aggrecanase, a catabolic mediator.


CONCLUSIONS
OP-1 may have a potential benefit in protecting articular cartilage during the development of OA.
Badlani
N
N
University of California, San Diego, Department of Orthopaedic Surgery, La Jolla, CA 92093-0630, USA.
Inoue
A
A
Healey
R
R
Coutts
R
R
Amiel
D
D
D053674:Aggrecans / Q000378:metabolism; D000818:Animals; D001169:Arthritis, Experimental / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D024043:Collagen Type II / Q000378:metabolism; D015870:Gene Expression; D020782:Matrix Metalloproteinases / Q000378:metabolism; D010003:Osteoarthritis / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D012333:RNA, Messenger / Q000235:genetics; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012720:Severity of Illness Index; D016212:Transforming Growth Factor beta / Q000494:pharmacology / Q000627:therapeutic use*
D053674:Aggrecans; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D024043:Collagen Type II; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D020782:Matrix Metalloproteinases