The antimicrobial peptide,LL-37,inhibits in vitro osteoclastogenesis

Uncoupled bone resorption leads to net alveolar bone loss in periodontitis. the deficiency of ll-37,the only human antimicrobial peptide in the cathelicidin family,in patients with aggressive periodontitis suggests that ll-37 may play a pivotal role in the inhibition of alveolar bone destruction in periodontitis. we aimed to investigate a novel function of ll-37 in osteoimmunity by blocking osteoclastogenesis in vitro. human osteoclast progenitor cells were isolated from a buffy coat of blood samples. the cells were cultured in the presence of various concentrations of ll-37 during an in vitro induction of osteoclastogenesis. non-toxic doses of ll-37 could block multinuclear formation of the progenitor cells and significantly diminish the number of tartrate-resistant acid-phosphatase-positive cells and the formation of resorption pits (p < 0.05),whereas these concentrations induced cellular proliferation,as demonstrated by increased expression of proliferating cell nuclear antigen. expression of several osteoclast genes was down-regulated by ll-37 treatment. it was demonstrated that nuclear translocation of nuclear-factor-activated t-cells 2 (nfat2) was blocked by ll-37 treatment,consistent with a significant reduction in the calcineurin activity (p < 0.005). collectively,our findings demonstrate that ll-37 inhibits the in vitro osteoclastogenesis by inhibiting the calcineurin activity,thus preventing nuclear translocation of nfat2.abbreviations: calcr,calcitonin receptor; clc-7,chloride-proton exchanger; ctsk,cathepsin k; dapi,4?,6-diamidino-2- phenylindole; egta,ethylene glycol tetraacetic acid; gapdh,glyceraldehyde-3-phosphate dehydrogenase; m-csf/csf1,macrophage-colony- stimulating factor; mmp-9,matrix metalloproteinase-9; mtt,[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide]; nfat2,nuclear factor of activated t-cells 2; pbs,phosphate-buffered saline; pcna,proliferating cell nuclear antigen; pcr,polymerase chain reaction; rank,receptor activator of nuclear factor kappa-b; rankl,receptor activator of nuclear factor kappa-b ligand; rt-pcr,reverse-transcription polymerase chain-reaction; tbs,tris-buffered saline; tcirg1,t-cell,immune regulator 1,atpase,h+ transporting,lysosomal v0 subunit a3; tracp,tartrate-resistant acid phosphatase. © 2012 international & american associations for dental research.