We developed two novel bovine lactoferrin (bLF) peptides to prevent alveolar bone destruction associated with periodontitis; one is bLF-2 targeting bLF-tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) binding site and the other peptide is bLF-3 binding to the TRAF6 dimerization area, competitively.
The topical application of these novel peptides markedly inhibited TNF-αexpression in gingival tissue (Fig.6-1～8) and significantly reduced the cathepsin-positive osteoclast number (Fig.7) by downregulating RANKL and upregulating OPG in the periodontal ligament in LPS-induced alveolar bone destruction model of rat. It is indicated that novel bLF peptides can be used to treat periodontitis-associated bone destruction.
See details in Yamada, et. al. (2024) Chem Biol Drug Des.
Sakura Yamada, Chanbora Chea, Hisako Furusho, Kanae Oda, Fumie Shiba, Kotaro Tanimoto, Shin-Ichi Tate, Mutsumi Miyauchi, Takashi Takata (2024) Effects of novel lactoferrin peptides on LPS-induced alveolar bone destruction in a rat model., Chemical biology & drug design, Volume 104, Number 1, pp. e14574
Published in 2024 Jul
(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-kappaB 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-alpha and interleukin-1beta expression in ST2 cells. Additionally, these peptides inhibited and reversed LPS-induced receptor activator of NF-kappaB 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.(MeSH Terms)