Studies of limitin as a therapeutic agent for periodontitis : analysis of mechanisms of inhibition of osteoclastogenesis

2007 Fiscal Year Final Research Report Summary

• Project/Area Number: 18592007
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Morphological basic dentistry
• Research Institution: Meikai University
• Principal Investigator: SATO Takuya Meikai University, School of Dentistry, Lecturer (00316689)
• Project Period (FY): 2006 – 2007
• Keywords: limitin / type-linterferon / osteoclasts / periodontitis

Research Abstract

Interferon (IFN)-ζ/limitin, a type-I IFN, utilizes the same IFN-α/β receptor as other type-I IFNs in mice. Here we examined the effects of IFN-ζ/limitin on osteoclastogenesis in vitro. IFN-C/limitin inhibited osteoclastogenesis from mouse macrophage osteoclast precursors induced by soluble receptor activator of NF-KB ligand (sRANKL) or tumor necrosis factor-a (TNF-α). IFN-C/limit in stimulated RNA-dependent protein kinase R (PKR) mRNA expression and decreased c-Fos protein production without affecting the c-Fos mRNA level in osteoclast precursors. Consistent with the decreased production of c-Fos protein, IFN-C/limitin decreased nuclear factor of activated T cells c1 (NFATc1) mRNA expression. Moreover, PKR knock-down partially restored the osteoclastogenesis inhibited by IFN-C/limit in. On the other hand, distinct from its effect on osteoclast precursors, IFN-ζ/limitin did not influence proliferation of anti-CD3 antibody-activated mouse T cells or their expression of NFATc1 mRNA or production of RANKL and TNF-α, suggesting a more restricted cell-type specificity compared with IFN-α and -β.
Recent change of IFN-C/limit in production lot showed more efficient inhibitory effects on osteoclastogenesis. Therefore, does dependent effects of IFN-C/limitin on osteoclastogenesis, mRNA expressions of NFATc1, c-Fos and PKR were re-examined. The data showed on 1000 times higher efficiencies. In addition, effects of IFN-C/limit in and IFN-β compared. The results showed that IFN-C/limit in were more potent inhibitor of osteoclastogenesis than other type-I IFNs.