title: The antimicrobial peptide, LL-37, inhibits in vitro osteoclastogenesis.
abstract: 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.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: C
authors.initials: C
authors.lastname: Supanchart
authors.forename: S
authors.initials: S
authors.lastname: Thawanaphong
authors.forename: A
authors.initials: A
authors.lastname: Makeudom
authors.forename: J G
authors.initials: JG
authors.lastname: Bolscher
authors.forename: K
authors.initials: K
authors.lastname: Nazmi
authors.forename: U
authors.initials: U
authors.lastname: Kornak
authors.forename: S
authors.initials: S
authors.lastname: Krisanaprakornkit
mesh_terms: D016301:Alveolar Bone Loss / Q000517:prevention & control*; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D065095:Calcineurin Inhibitors; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D050778:NFATC Transcription Factors / Q000502:physiology; D010010:Osteoclasts / Q000187:drug effects*; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D065095:Calcineurin Inhibitors; D050778:NFATC Transcription Factors; D018809:Proliferating Cell Nuclear Antigen; D016173:Macrophage Colony-Stimulating Factor; D054804:Cathelicidins