Human Beta-Defensin-1 Promotes Osteoclastogenesis via the p44/42 Mitogen-Activated Protein Kinases
Objectives: The objectives of this study were to investigate the enhancing effect of human beta-defensin-1 (hBD-1) on osteoclast formation and function and to elucidate the involved signaling pathway in vitro. Methods: Human peripheral blood mononuclear cells (PBMCs) were first incubated with various doses of hBD-1 and cell viability was assayed by MTT. PBMCs were treated with macrophage-colony stimulating factor and receptor activator of nuclear factor kappa-B ligand (RANKL) in the presence or absence of non-toxic doses of hBD-1. In vitro osteoclastogenesis was analyzed by tartrate-resistant acid phosphatase (TRAP) staining, osteoclast-specific gene expression, and a resorption pit assay. Involvement of mitogen-activated protein kinases (MAPKs) was studied by immunoblotting and specific MAPK inhibitors. Results: HBD-1 potentiated induction of in vitro osteoclastogenesis by RANKL, as shown by significantly increased number of TRAP-positive multinuclear cells and resorption areas on the dentin slices and further up-regulated expressions of osteoclast-specific genes, compared to those by RANKL treatment (p<0.05). However, hBD-1 treatment without RANKL failed to induce formation of osteoclast-like cells. A significant and further increase in transient phosphorylation of the p44/42 MAPKs was found by hBD-1 co-treatment (p<0.05), consistent with the inhibitory effect of pretreatment with U0126 and PD98059 on hBD-1-enhanced osteoclastogenesis. Conclusions: Taken together, hBD-1 potentiates the induction of in vitro osteoclastogenesis by RANKL via enhanced phosphorylation of the p44/42 MAPKs.
South East Asian Division Meeting
2017 South East Asian Division Meeting (Taipei, Taiwan) Taipei, Taiwan
2017 0043 Craniofacial Biology
Makeudom, Anupong
( Faculty of Associated Medical Sciences, Chiang Mai University
, Chiang Mai
, Thailand
)
Supanchart, Chayarop
( Faculty of Dentistry, Chiang Mai University
, Chiang Mai
, Thailand
)
Montreekachon, Pattanin
( Faculty of Dentistry, Chiang Mai University
, Chiang Mai
, Thailand
)
Sastraruji, Thanapat
( Faculty of Dentistry, Chiang Mai University
, Chiang Mai
, Thailand
)
Krisanaprakornkit, Suttichai
( Faculty of Dentistry, Chiang Mai University
, Chiang Mai
, Thailand
)
Royal Golden Jubilee-Thailand Research Fund (PHD/0051/2556); Thailand Research Fund (#BRG6080001)
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