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 i...

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Main Authors: Supanchart C., Thawanaphong S., Makeudom A., Bolscher J.G., Nazmi K., Kornak U., Krisanaprakornkit S.
Format: Article
Language:English
Published: 2014
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http://cmuir.cmu.ac.th/handle/6653943832/900
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spelling th-cmuir.6653943832-9002014-08-29T09:02:18Z The antimicrobial peptide, LL-37, inhibits in vitro osteoclastogenesis Supanchart C. Thawanaphong S. Makeudom A. Bolscher J.G. Nazmi K. Kornak U. Krisanaprakornkit S. 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. 2014-08-29T09:02:18Z 2014-08-29T09:02:18Z 2012 Article 220345 10.1177/0022034512460402 JDREA http://www.scopus.com/inward/record.url?eid=2-s2.0-84867728779&partnerID=40&md5=fbe2565f1947add9f29b2b13b1eed73d http://cmuir.cmu.ac.th/handle/6653943832/900 English
institution Chiang Mai University
building Chiang Mai University Library
country Thailand
collection CMU Intellectual Repository
language English
description 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.
format Article
author Supanchart C.
Thawanaphong S.
Makeudom A.
Bolscher J.G.
Nazmi K.
Kornak U.
Krisanaprakornkit S.
spellingShingle Supanchart C.
Thawanaphong S.
Makeudom A.
Bolscher J.G.
Nazmi K.
Kornak U.
Krisanaprakornkit S.
The antimicrobial peptide, LL-37, inhibits in vitro osteoclastogenesis
author_facet Supanchart C.
Thawanaphong S.
Makeudom A.
Bolscher J.G.
Nazmi K.
Kornak U.
Krisanaprakornkit S.
author_sort Supanchart C.
title The antimicrobial peptide, LL-37, inhibits in vitro osteoclastogenesis
title_short The antimicrobial peptide, LL-37, inhibits in vitro osteoclastogenesis
title_full The antimicrobial peptide, LL-37, inhibits in vitro osteoclastogenesis
title_fullStr The antimicrobial peptide, LL-37, inhibits in vitro osteoclastogenesis
title_full_unstemmed The antimicrobial peptide, LL-37, inhibits in vitro osteoclastogenesis
title_sort antimicrobial peptide, ll-37, inhibits in vitro osteoclastogenesis
publishDate 2014
url http://www.scopus.com/inward/record.url?eid=2-s2.0-84867728779&partnerID=40&md5=fbe2565f1947add9f29b2b13b1eed73d
http://cmuir.cmu.ac.th/handle/6653943832/900
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