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 μg 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 the first 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.