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...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2017-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5609750?pdf=render |
| _version_ | 1811327664666968064 |
|---|---|
| author | Yuki Ozaki Masanori Koide Yuriko Furuya Tadashi Ninomiya Hisataka Yasuda Midori Nakamura Yasuhiro Kobayashi Naoyuki Takahashi Nobuo Yoshinari Nobuyuki Udagawa |
| author_facet | Yuki Ozaki Masanori Koide Yuriko Furuya Tadashi Ninomiya Hisataka Yasuda Midori Nakamura Yasuhiro Kobayashi Naoyuki Takahashi Nobuo Yoshinari Nobuyuki Udagawa |
| author_sort | Yuki Ozaki |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-13T15:12:01Z |
| format | Article |
| id | doaj.art-2487bcb9da944fa09fe246d8594a0abf |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T15:12:01Z |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-2487bcb9da944fa09fe246d8594a0abf2022-12-22T02:41:58ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01129e018490410.1371/journal.pone.0184904Treatment of OPG-deficient mice with WP9QY, a RANKL-binding peptide, recovers alveolar bone loss by suppressing osteoclastogenesis and enhancing osteoblastogenesis.Yuki OzakiMasanori KoideYuriko FuruyaTadashi NinomiyaHisataka YasudaMidori NakamuraYasuhiro KobayashiNaoyuki TakahashiNobuo YoshinariNobuyuki UdagawaOsteoblasts 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.http://europepmc.org/articles/PMC5609750?pdf=render |
| spellingShingle | Yuki Ozaki Masanori Koide Yuriko Furuya Tadashi Ninomiya Hisataka Yasuda Midori Nakamura Yasuhiro Kobayashi Naoyuki Takahashi Nobuo Yoshinari Nobuyuki Udagawa Treatment of OPG-deficient mice with WP9QY, a RANKL-binding peptide, recovers alveolar bone loss by suppressing osteoclastogenesis and enhancing osteoblastogenesis. PLoS ONE |
| 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 |
| url | http://europepmc.org/articles/PMC5609750?pdf=render |
| work_keys_str_mv | AT yukiozaki treatmentofopgdeficientmicewithwp9qyaranklbindingpeptiderecoversalveolarbonelossbysuppressingosteoclastogenesisandenhancingosteoblastogenesis AT masanorikoide treatmentofopgdeficientmicewithwp9qyaranklbindingpeptiderecoversalveolarbonelossbysuppressingosteoclastogenesisandenhancingosteoblastogenesis AT yurikofuruya treatmentofopgdeficientmicewithwp9qyaranklbindingpeptiderecoversalveolarbonelossbysuppressingosteoclastogenesisandenhancingosteoblastogenesis AT tadashininomiya treatmentofopgdeficientmicewithwp9qyaranklbindingpeptiderecoversalveolarbonelossbysuppressingosteoclastogenesisandenhancingosteoblastogenesis AT hisatakayasuda treatmentofopgdeficientmicewithwp9qyaranklbindingpeptiderecoversalveolarbonelossbysuppressingosteoclastogenesisandenhancingosteoblastogenesis AT midorinakamura treatmentofopgdeficientmicewithwp9qyaranklbindingpeptiderecoversalveolarbonelossbysuppressingosteoclastogenesisandenhancingosteoblastogenesis AT yasuhirokobayashi treatmentofopgdeficientmicewithwp9qyaranklbindingpeptiderecoversalveolarbonelossbysuppressingosteoclastogenesisandenhancingosteoblastogenesis AT naoyukitakahashi treatmentofopgdeficientmicewithwp9qyaranklbindingpeptiderecoversalveolarbonelossbysuppressingosteoclastogenesisandenhancingosteoblastogenesis AT nobuoyoshinari treatmentofopgdeficientmicewithwp9qyaranklbindingpeptiderecoversalveolarbonelossbysuppressingosteoclastogenesisandenhancingosteoblastogenesis AT nobuyukiudagawa treatmentofopgdeficientmicewithwp9qyaranklbindingpeptiderecoversalveolarbonelossbysuppressingosteoclastogenesisandenhancingosteoblastogenesis |