High level of interleukin-32 gamma in the joint of ankylosing spondylitis is associated with osteoblast differentiation

초록

Backgound: The formation of bony spurs and ankylosis is a key pathognomic feature in ankylosing spondylitis (AS) and results in functional impairment. The aim of this study was to investigate the role of IL-32 gamma in osteoblast (OB) differentiation and its association with the pathogenesis of AS. Methods: The concentration and expression of IL-32 gamma were evaluated in synovial fluid and tissue from patients with AS, rheumatoid arthritis (RA) and osteoarthritis (OA), using enzyme-linked immunosorbent assay and immunohistochemistry. To establish whether IL-32 gamma affects OB differentiation, we used calvarial cells of IL-32 gamma transgenic (TG) mice or wild-type (WT) mice. To elucidate the mechanism of osteoblastogenesis, levels of regulators were assayed in IL-32 gamma TG mice and in primary OBs after IL-32 gamma stimulation. Results: The IL-32 gamma levels were higher in the synovial fluid of AS patients compared with RA or OA patients and the expression of IL-32 was higher in AS synovia than in RA or OA synovia. Additional IL-32 gamma stimulation in precursor cells enhanced OB differentiation potentially and IL-32 gamma TG mice showed higher rates of OB differentiation than WT mice. IL-32 gamma reduced the expression of DKK-1, a negative regulator, in both WT precursor cells and human OBs and the constitutive expression of DKK-1 was suppressed in calvarial cells from IL-32 gamma TG mice. Conclusions: The elevated level of IL-32 gamma in AS joint could enhance OB differentiation via DKK-1 suppression. Therefore, IL-32 gamma might be a putative molecular target to prevent the abnormal bone formation in AS.

키워드