[Inhibition of cartilage destruction in collagen-induced arthritis by altered CII 263-272 peptide: experiment with rats].
OBJECTIVE
To study the inhibitory effect of altered collagen II (CII) 263-272 peptide (sub268-270) with three consecutive substitutions of TCR-contacting residues on joint inflammation and cartilage destruction in collagen-induced arthritis (CIA).


METHODS
Thirty-two Lewis rats were injected intracutaneously with bovine collagen type II so as to establish models of arthritis and then were randomly divided into 4 equal groups to be injected intravenously with sub268-270 30 microg, 5 microg, or 1 microg and PBS twice a week for 3 weeks. The therapeutic effect of the altered peptide on arthritis was evaluated by arthritis score. After the treatment the rats were killed and their ankle joints were taken to undergo pathological examination to observe the existence of synovitis, pannus formation, cartilage damage, and bone erosion. Blood samples were collected to detect the serum cartilage oligomeric matrix protein (COMP). Cartilage proteoglycan-specific dye safranin O was used on the joint sections to observe the coloration of the dye in the cartilage.


RESULTS
The arthritis score in rats treated by 30 microg altered CII peptide was (5.6 +/- 2.63), significantly lower than those of the 5 microg, 1 microg, and blank control groups [(9.67 +/- 5.61), (10.02 +/- 5.06), and (11.8 +/- 5.34) respectively, all P < 0.01]. The synovitis score of the 30 microg group was (1.11 +/- 0.43), significantly lower than those of the 5 microg, 1 microg, and blank control groups [(1.87 +/- 0.78), (2.11 +/- 0.83), and (2.25 +/- 0.73) respectively, all P < 0.01]. The pannus score of the 30 microg group was (1.11 +/- 0.43), significantly lower than those of the 5 microg, 1 microg, and blank control groups [(1.83 +/- 0.79), (2.07 +/- 0.91), and (2.27 +/- 0.71) respectively, all P < 0.01]. The cartilage damage score of the 30 microg group was 0.56 +/- 0.23), significantly lower than those of the 5 microg, 1 microg, and blank control groups [(1.91 +/- 0.83), (2.13 +/- 0.79), and (2.29 +/- 0.69) respectively, all P < 0.01]. The bone erosion score of the 30 microg group was (0.53 +/- 0.21), significantly lower than those of the 5 microg, 1 microg, and blank control groups [(1.71 +/- 0.67), (1.88 +/- 0.93), and (2.01 +/- 0.93) respectively, all P < 0.01]. The serum COMP of the 30 microg group was (2.21 +/- 0.76), significantly lower than those of the 5 microg, 1 microg, and blank control groups [(5.63 +/- 1.73), (6.04 +/- 1.76), and (7.00 +/- 1.46) respectively, all P < 0.01]. The content of safranin O (A value) in the joint section of the 30 microg group was (2.35 +/- 0.76), significantly higher than those of the 5 microg, 1 microg, and blank control groups [(1.57 +/- 0.63), (1.37 +/- 0.53), and (1.00 +/- 0.41) respectively, all P < 0.01].


CONCLUSIONS
The altered CII peptide sub268-270 effectively ameliorates CIA and inhibits the cartilage damage in CIA, and may modify the disease course of rheumatoid arthritis.
Yao
Zhong-qiang
ZQ
Department of Rheumatology & Immunology, People's Hospital, Beijing University, Beijing 100044, China.
Zhao
Jin-xia
JX
Li
Ru
R
Li
Zhan-guo
ZG
D000818:Animals; D001169:Arthritis, Experimental / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002417:Cattle; D024043:Collagen Type II / Q000737:chemistry / Q000494:pharmacology*; D016326:Extracellular Matrix Proteins / Q000097:blood; D006023:Glycoproteins / Q000097:blood; D006651:Histocytochemistry; D008297:Male; D064235:Matrilin Proteins; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D011509:Proteoglycans / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew
D024043:Collagen Type II; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D064235:Matrilin Proteins; D010446:Peptide Fragments; D011509:Proteoglycans