title: The antimicrobial peptide LL37 promotes bone regeneration in a rat calvarial bone defect.
abstract: LL37, an antimicrobial peptide, exhibits multiple bio-functions in various types of cells, including migration, cytokine production, apoptosis, and angiogenesis. Neovascularization and the subsequent recruitment of stem cells are essential for tissue engineering therapy, including bone regeneration. We hypothesized that LL37 can facilitate successful bone regeneration. To prove this hypothesis, the present study tested the effects of LL37 on bone formation in a rat calvarial bone defect model. Synthesized LL37 markedly induced newly formed bone. Interestingly, morphologically fibroblastic cells were observed in animals treated with LL37 on day 7, the early stage of tissue regeneration, which were positive for STRO-1, a marker of mesenchymal stem cells (MSCs), and accumulated in the bone defect area where cells positive for CD34, a marker of endothelial cells, were also localized. In addition, LL37 stimulated tube formation by endothelial cells and the proliferation of MSCs in vitro. These findings demonstrated for the first time that LL37 can regulate angiogenesis and the recruitment of stem cells to promote bone regeneration.
authors.affiliation: Department of Periodontal Medicine, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
authors.forename: Mizuho
authors.initials: M
authors.lastname: Kittaka
authors.forename: Hideki
authors.initials: H
authors.lastname: Shiba
authors.forename: Mikihito
authors.initials: M
authors.lastname: Kajiya
authors.forename: Takako
authors.initials: T
authors.lastname: Fujita
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Iwata
authors.forename: Khung
authors.initials: K
authors.lastname: Rathvisal
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Ouhara
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Takeda
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Fujita
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Komatsuzawa
authors.forename: Hidemi
authors.initials: H
authors.lastname: Kurihara
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D000954:Antigens, Surface / Q000378:metabolism; D023181:Antimicrobial Cationic Peptides; D001861:Bone Regeneration / Q000502:physiology*; D054804:Cathelicidins / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D018919:Neovascularization, Physiologic; D010012:Osteogenesis / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D012886:Skull / Q000002:abnormalities / Q000378:metabolism*; D023822:Tissue Engineering
chemical_list: D018952:Antigens, CD34; D000954:Antigens, Surface; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; C527498:STRO-1 antigen, rat
keywords: Angiogenesis; Bone regeneration; LL37