Cargando…
Treatment of OPG-deficient mice with WP9QY, a RANKL-binding peptide, recovers alveolar bone loss by suppressing osteoclastogenesis and enhancing osteoblastogenesis
Osteoblasts express two key molecules for osteoclast differentiation, receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG), a soluble decoy receptor for RANKL. RANKL induces osteoclastogenesis, while OPG inhibits it by blocking the binding of RANKL to RANK, a cellular receptor of RAN...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5609750/ https://www.ncbi.nlm.nih.gov/pubmed/28937990 http://dx.doi.org/10.1371/journal.pone.0184904 |
_version_ | 1783265660065808384 |
---|---|
author | Ozaki, Yuki Koide, Masanori Furuya, Yuriko Ninomiya, Tadashi Yasuda, Hisataka Nakamura, Midori Kobayashi, Yasuhiro Takahashi, Naoyuki Yoshinari, Nobuo Udagawa, Nobuyuki |
author_facet | Ozaki, Yuki Koide, Masanori Furuya, Yuriko Ninomiya, Tadashi Yasuda, Hisataka Nakamura, Midori Kobayashi, Yasuhiro Takahashi, Naoyuki Yoshinari, Nobuo Udagawa, Nobuyuki |
author_sort | Ozaki, Yuki |
collection | PubMed |
description | Osteoblasts express two key molecules for osteoclast differentiation, receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG), a soluble decoy receptor for RANKL. RANKL induces osteoclastogenesis, while OPG inhibits it by blocking the binding of RANKL to RANK, a cellular receptor of RANKL. OPG-deficient (OPG(–/–)) mice exhibit severe alveolar bone loss with enhanced bone resorption. WP9QY (W9) peptide binds to RANKL and blocks RANKL-induced osteoclastogenesis. W9 is also reported to stimulate bone formation in vivo. Here, we show that treatment with W9 restores alveolar bone loss in OPG(–/–)mice by suppressing osteoclastogenesis and enhancing osteoblastogenesis. Administration of W9 or risedronate, a bisphosphonate, to OPG(–/–)mice significantly decreased the osteoclast number in the alveolar bone. Interestingly, treatment with W9, but not risedronate, enhanced Wnt/β-catenin signaling and induced alveolar bone formation in OPG(–/–)mice. Expression of sclerostin, an inhibitor of Wnt/β-catenin signaling, was significantly lower in tibiae of OPG(–/–)mice than in wild-type mice. Treatment with risedronate recovered sclerostin expression in OPG(–/–)mice, while W9 treatment further suppressed sclerostin expression. Histomorphometric analysis confirmed that bone formation-related parameters in OPG(–/–)mice, such as osteoblast number, osteoblast surface and osteoid surface, were increased by W9 administration but not by risedronate administration. These results suggest that treatment of OPG(–/–)mice with W9 suppressed osteoclastogenesis by inhibiting RANKL signaling and enhanced osteoblastogenesis by attenuating sclerostin expression in the alveolar bone. Taken together, W9 may be a useful drug to prevent alveolar bone loss in periodontitis. |
format | Online Article Text |
id | pubmed-5609750 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-56097502017-10-09 Treatment of OPG-deficient mice with WP9QY, a RANKL-binding peptide, recovers alveolar bone loss by suppressing osteoclastogenesis and enhancing osteoblastogenesis Ozaki, Yuki Koide, Masanori Furuya, Yuriko Ninomiya, Tadashi Yasuda, Hisataka Nakamura, Midori Kobayashi, Yasuhiro Takahashi, Naoyuki Yoshinari, Nobuo Udagawa, Nobuyuki PLoS One Research Article Osteoblasts express two key molecules for osteoclast differentiation, receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG), a soluble decoy receptor for RANKL. RANKL induces osteoclastogenesis, while OPG inhibits it by blocking the binding of RANKL to RANK, a cellular receptor of RANKL. OPG-deficient (OPG(–/–)) mice exhibit severe alveolar bone loss with enhanced bone resorption. WP9QY (W9) peptide binds to RANKL and blocks RANKL-induced osteoclastogenesis. W9 is also reported to stimulate bone formation in vivo. Here, we show that treatment with W9 restores alveolar bone loss in OPG(–/–)mice by suppressing osteoclastogenesis and enhancing osteoblastogenesis. Administration of W9 or risedronate, a bisphosphonate, to OPG(–/–)mice significantly decreased the osteoclast number in the alveolar bone. Interestingly, treatment with W9, but not risedronate, enhanced Wnt/β-catenin signaling and induced alveolar bone formation in OPG(–/–)mice. Expression of sclerostin, an inhibitor of Wnt/β-catenin signaling, was significantly lower in tibiae of OPG(–/–)mice than in wild-type mice. Treatment with risedronate recovered sclerostin expression in OPG(–/–)mice, while W9 treatment further suppressed sclerostin expression. Histomorphometric analysis confirmed that bone formation-related parameters in OPG(–/–)mice, such as osteoblast number, osteoblast surface and osteoid surface, were increased by W9 administration but not by risedronate administration. These results suggest that treatment of OPG(–/–)mice with W9 suppressed osteoclastogenesis by inhibiting RANKL signaling and enhanced osteoblastogenesis by attenuating sclerostin expression in the alveolar bone. Taken together, W9 may be a useful drug to prevent alveolar bone loss in periodontitis. Public Library of Science 2017-09-22 /pmc/articles/PMC5609750/ /pubmed/28937990 http://dx.doi.org/10.1371/journal.pone.0184904 Text en © 2017 Ozaki et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Ozaki, Yuki Koide, Masanori Furuya, Yuriko Ninomiya, Tadashi Yasuda, Hisataka Nakamura, Midori Kobayashi, Yasuhiro Takahashi, Naoyuki Yoshinari, Nobuo Udagawa, Nobuyuki Treatment of OPG-deficient mice with WP9QY, a RANKL-binding peptide, recovers alveolar bone loss by suppressing osteoclastogenesis and enhancing osteoblastogenesis |
title | Treatment of OPG-deficient mice with WP9QY, a RANKL-binding peptide, recovers alveolar bone loss by suppressing osteoclastogenesis and enhancing osteoblastogenesis |
title_full | Treatment of OPG-deficient mice with WP9QY, a RANKL-binding peptide, recovers alveolar bone loss by suppressing osteoclastogenesis and enhancing osteoblastogenesis |
title_fullStr | Treatment of OPG-deficient mice with WP9QY, a RANKL-binding peptide, recovers alveolar bone loss by suppressing osteoclastogenesis and enhancing osteoblastogenesis |
title_full_unstemmed | Treatment of OPG-deficient mice with WP9QY, a RANKL-binding peptide, recovers alveolar bone loss by suppressing osteoclastogenesis and enhancing osteoblastogenesis |
title_short | Treatment of OPG-deficient mice with WP9QY, a RANKL-binding peptide, recovers alveolar bone loss by suppressing osteoclastogenesis and enhancing osteoblastogenesis |
title_sort | treatment of opg-deficient mice with wp9qy, a rankl-binding peptide, recovers alveolar bone loss by suppressing osteoclastogenesis and enhancing osteoblastogenesis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5609750/ https://www.ncbi.nlm.nih.gov/pubmed/28937990 http://dx.doi.org/10.1371/journal.pone.0184904 |
work_keys_str_mv | AT ozakiyuki treatmentofopgdeficientmicewithwp9qyaranklbindingpeptiderecoversalveolarbonelossbysuppressingosteoclastogenesisandenhancingosteoblastogenesis AT koidemasanori treatmentofopgdeficientmicewithwp9qyaranklbindingpeptiderecoversalveolarbonelossbysuppressingosteoclastogenesisandenhancingosteoblastogenesis AT furuyayuriko treatmentofopgdeficientmicewithwp9qyaranklbindingpeptiderecoversalveolarbonelossbysuppressingosteoclastogenesisandenhancingosteoblastogenesis AT ninomiyatadashi treatmentofopgdeficientmicewithwp9qyaranklbindingpeptiderecoversalveolarbonelossbysuppressingosteoclastogenesisandenhancingosteoblastogenesis AT yasudahisataka treatmentofopgdeficientmicewithwp9qyaranklbindingpeptiderecoversalveolarbonelossbysuppressingosteoclastogenesisandenhancingosteoblastogenesis AT nakamuramidori treatmentofopgdeficientmicewithwp9qyaranklbindingpeptiderecoversalveolarbonelossbysuppressingosteoclastogenesisandenhancingosteoblastogenesis AT kobayashiyasuhiro treatmentofopgdeficientmicewithwp9qyaranklbindingpeptiderecoversalveolarbonelossbysuppressingosteoclastogenesisandenhancingosteoblastogenesis AT takahashinaoyuki treatmentofopgdeficientmicewithwp9qyaranklbindingpeptiderecoversalveolarbonelossbysuppressingosteoclastogenesisandenhancingosteoblastogenesis AT yoshinarinobuo treatmentofopgdeficientmicewithwp9qyaranklbindingpeptiderecoversalveolarbonelossbysuppressingosteoclastogenesisandenhancingosteoblastogenesis AT udagawanobuyuki treatmentofopgdeficientmicewithwp9qyaranklbindingpeptiderecoversalveolarbonelossbysuppressingosteoclastogenesisandenhancingosteoblastogenesis |