RRC ID 81447
Author Yamada S, Chea C, Furusho H, Oda K, Shiba F, Tanimoto K, Tate SI, Miyauchi M, Takata T.
Title Effects of novel lactoferrin peptides on LPS-induced alveolar bone destruction in a rat model.
Journal Chem Biol Drug Des
Abstract To develop novel bovine lactoferrin (bLF) peptides targeting bLF-tumour necrosis factor (TNF) receptor-associated factor 6 (TRAF6) binding sites, we identified two peptides that could target bLF-TRAF6 binding sites using structural analysis. Moreover, another peptide that could bind to the TRAF6 dimerization area was selected from the bLF sequence. The effects of each peptide on cytokine expression in lipopolysaccharide (LPS)-stimulated osteoblasts (ST2) and on osteoclastogenesis were examined using an LPS-treated co-culture of primary bone marrow cells (BMCs) with ST2 cells and a single culture of osteoclast precursor cells (RAW-D) treated with soluble receptor activator of NF-κB ligand. Finally, the effectiveness of these peptides against LPS-induced alveolar bone destruction was assessed. Two of the three peptides significantly suppressed LPS-induced TNF-α and interleukin-1β expression in ST2 cells. Additionally, these peptides inhibited and reversed LPS-induced receptor activator of NF-κB ligand (RANKL) upregulation and osteoprotegerin (OPG) downregulation, respectively. Furthermore, both peptides significantly reduced LPS-induced osteoclastogenesis in the BMC-ST2 co-culture and RANKL-induced osteoclastogenesis in RAW-D cells. In vivo, topical application of these peptides significantly reduced the osteoclast number by downregulating RANKL and upregulating OPG in the periodontal ligament. It is indicated that the novel bLF peptides can be used to treat periodontitis-associated bone destruction.
Volume 104(1)
Pages e14574
Published 2024-7-1
DOI 10.1111/cbdd.14574
PMID 38958121
MeSH Alveolar Bone Loss / drug therapy Alveolar Bone Loss / metabolism Alveolar Bone Loss / pathology Animals Binding Sites Cattle Coculture Techniques Disease Models, Animal Lactoferrin* / chemistry Lactoferrin* / metabolism Lactoferrin* / pharmacology Lipopolysaccharides* / pharmacology Male Mice Osteoblasts / cytology Osteoblasts / drug effects Osteoblasts / metabolism Osteoclasts* / drug effects Osteoclasts* / metabolism Osteogenesis / drug effects Osteoprotegerin / metabolism Peptides* / chemistry Peptides* / pharmacology RANK Ligand / metabolism Rats Rats, Sprague-Dawley Tumor Necrosis Factor-alpha / metabolism
Resource
Human and Animal Cells RAW-D cell(RCB5503)