YKL-39, a human cartilage-related protein, induces arthritis in mice.
OBJECTIVE
To determine whether YKL-39, a recently cloned secretory protein of articular chondrocytes, is arthritogenic in mice.


METHODS
Recombinant YKL-39 (rYKL-39) was expressed and purified from E. coli. To induce arthritis in mice, rYKL-39 (1, 10 or 50 g in Freund's incomplete adjuvant) was injected into the right footpad of mice from four different strains (BALB/c, DBA/1J, C57BL/6 and ICR). The mice received a second immunization with rYKL-39 by intradermal injection into the root of the tail 10 days after the first immunization. Severity of arthritis was assessed by scoring each paw on a scale from 0 to 4. Sixty days after thefirst immunization, the mice were sacrificed and the joints were examined by immunohistochemistry and radiography. The anti-YKL-39 and anti type II-collagen (CII) antibody titres were also assayed using ELISA.


RESULTS
Immunization with YKL-39 induced arthritis in all strains of mice tested, among which BALB/c was most susceptible. Histological examination showed synovial proliferation and irregularity of the cartilage surface in YKL-39-injected BALB/c mice. Moreover radiographic analysis revealed pathological changes in these mice. The YKL-39-immunised mice produced not only anti-YKL-39 antibody but also antibody against type II collagen, suggesting a spreading of autoimmunity after YKL-39.


CONCLUSIONS
YKL-39, a cartilage-related protein, is found to induce arthritis accompanied by pathologic changes in bone and cartilage. A better understanding of the immune response against cartilage-related components including YKL-39 may help to elucidate the pathological processes of arthritic disorders.
Sakata
M
M
Rheumatology, Immunology, and Genetics Program, Institute of Medical Science, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan.
Masuko-Hongo
K
K
Tsuruha
J
J
Sekine
T
T
Nakamura
H
H
Takigawa
M
M
Nishioka
K
K
Kato
T
T
D054392:Adipokines; D000818:Animals; D000906:Antibodies / Q000097:blood; D000918:Antibody Specificity; D001169:Arthritis, Experimental / Q000000981:diagnostic imaging / Q000276:immunology* / Q000473:pathology; D002356:Cartilage; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D000071451:Chitinase-3-Like Protein 1; D024043:Collagen Type II / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D006801:Humans; D007271:Injections, Intradermal; D037102:Lectins; D007963:Leukocytes, Mononuclear / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008813:Mice, Inbred ICR; D011859:Radiography; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology
D054392:Adipokines; D000906:Antibodies; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D024043:Collagen Type II; D006023:Glycoproteins; D037102:Lectins; D011994:Recombinant Proteins