p57Kip2 is an essential regulator of vitamin D receptor-dependent mechanisms.
A cyclin-dependent kinase (CDK) inhibitor, p57Kip2, is an important molecule involved in bone development; p57Kip2-deficient (p57-/-) mice display neonatal lethality resulting from abnormal bone formation and cleft palate. The modulator 1α,25-dihydroxyvitamin D3 (l,25-(OH)2VD3) has shown the potenti...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2023-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0276838 |
| _version_ | 1797901821336879104 |
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| author | Katsuhiko Takahashi Hitoshi Amano Tomohiko Urano Minqi Li Meiko Oki Kazuhiro Aoki Norio Amizuka Keiichi I Nakayama Keiko Nakayama Nobuyuki Udagawa Nobuaki Higashi |
| author_facet | Katsuhiko Takahashi Hitoshi Amano Tomohiko Urano Minqi Li Meiko Oki Kazuhiro Aoki Norio Amizuka Keiichi I Nakayama Keiko Nakayama Nobuyuki Udagawa Nobuaki Higashi |
| author_sort | Katsuhiko Takahashi |
| collection | DOAJ |
| description | A cyclin-dependent kinase (CDK) inhibitor, p57Kip2, is an important molecule involved in bone development; p57Kip2-deficient (p57-/-) mice display neonatal lethality resulting from abnormal bone formation and cleft palate. The modulator 1α,25-dihydroxyvitamin D3 (l,25-(OH)2VD3) has shown the potential to suppress the proliferation and induce the differentiation of normal and tumor cells. The current study assessed the role of p57Kip2 in the 1,25-(OH)2VD3-regulated differentiation of osteoblasts because p57Kip2 is associated with the vitamin D receptor (VDR). Additionally, 1,25-(OH)2VD3 treatment increased p57KIP2 expression and induced the colocalization of p57KIP2 with VDR in the osteoblast nucleus. Primary p57-/- osteoblasts exhibited higher proliferation rates with Cdk activation than p57+/+ cells. A lower level of nodule mineralization was observed in p57-/- osteoblasts than in p57+/+ cells. In p57+/+ osteoblasts, 1,25-(OH)2VD3 upregulated the p57Kip2 and opn mRNA expression levels, while the opn expression levels were significantly decreased in p57-/- cells. The osteoclastogenesis assay performed using bone marrow cocultured with 1,25-(OH)2VD3-treated osteoblasts revealed a decreased efficiency of 1,25-(OH)2VD3-stimulated osteoclastogenesis in p57-/- cells. Based on these results, p57Kip2 might function as a mediator of 1,25-(OH)2VD3 signaling, thereby enabling sufficient VDR activation for osteoblast maturation. |
| first_indexed | 2024-04-10T09:08:00Z |
| format | Article |
| id | doaj.art-b55c3f43ea194d928f3a51aa14617ed8 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-10T09:08:00Z |
| publishDate | 2023-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-b55c3f43ea194d928f3a51aa14617ed82023-02-21T05:31:44ZengPublic Library of Science (PLoS)PLoS ONE1932-62032023-01-01182e027683810.1371/journal.pone.0276838p57Kip2 is an essential regulator of vitamin D receptor-dependent mechanisms.Katsuhiko TakahashiHitoshi AmanoTomohiko UranoMinqi LiMeiko OkiKazuhiro AokiNorio AmizukaKeiichi I NakayamaKeiko NakayamaNobuyuki UdagawaNobuaki HigashiA cyclin-dependent kinase (CDK) inhibitor, p57Kip2, is an important molecule involved in bone development; p57Kip2-deficient (p57-/-) mice display neonatal lethality resulting from abnormal bone formation and cleft palate. The modulator 1α,25-dihydroxyvitamin D3 (l,25-(OH)2VD3) has shown the potential to suppress the proliferation and induce the differentiation of normal and tumor cells. The current study assessed the role of p57Kip2 in the 1,25-(OH)2VD3-regulated differentiation of osteoblasts because p57Kip2 is associated with the vitamin D receptor (VDR). Additionally, 1,25-(OH)2VD3 treatment increased p57KIP2 expression and induced the colocalization of p57KIP2 with VDR in the osteoblast nucleus. Primary p57-/- osteoblasts exhibited higher proliferation rates with Cdk activation than p57+/+ cells. A lower level of nodule mineralization was observed in p57-/- osteoblasts than in p57+/+ cells. In p57+/+ osteoblasts, 1,25-(OH)2VD3 upregulated the p57Kip2 and opn mRNA expression levels, while the opn expression levels were significantly decreased in p57-/- cells. The osteoclastogenesis assay performed using bone marrow cocultured with 1,25-(OH)2VD3-treated osteoblasts revealed a decreased efficiency of 1,25-(OH)2VD3-stimulated osteoclastogenesis in p57-/- cells. Based on these results, p57Kip2 might function as a mediator of 1,25-(OH)2VD3 signaling, thereby enabling sufficient VDR activation for osteoblast maturation.https://doi.org/10.1371/journal.pone.0276838 |
| spellingShingle | Katsuhiko Takahashi Hitoshi Amano Tomohiko Urano Minqi Li Meiko Oki Kazuhiro Aoki Norio Amizuka Keiichi I Nakayama Keiko Nakayama Nobuyuki Udagawa Nobuaki Higashi p57Kip2 is an essential regulator of vitamin D receptor-dependent mechanisms. PLoS ONE |
| title | p57Kip2 is an essential regulator of vitamin D receptor-dependent mechanisms. |
| title_full | p57Kip2 is an essential regulator of vitamin D receptor-dependent mechanisms. |
| title_fullStr | p57Kip2 is an essential regulator of vitamin D receptor-dependent mechanisms. |
| title_full_unstemmed | p57Kip2 is an essential regulator of vitamin D receptor-dependent mechanisms. |
| title_short | p57Kip2 is an essential regulator of vitamin D receptor-dependent mechanisms. |
| title_sort | p57kip2 is an essential regulator of vitamin d receptor dependent mechanisms |
| url | https://doi.org/10.1371/journal.pone.0276838 |
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