Anti–NF-κB peptide derived from nuclear acidic protein attenuates ovariectomy-induced osteoporosis in mice
NF-κB is a transcription factor that is activated with aging. It plays a key role in the development of osteoporosis by promoting osteoclast differentiation and inhibiting osteoblast differentiation. In this study, we developed a small anti–NF-κB peptide called 6A-8R from a nuclear acidic protein (a...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Clinical investigation
2023-11-01
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| Series: | JCI Insight |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/jci.insight.171962 |
| _version_ | 1797634233694420992 |
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| author | Kenji Takami Kazuki Okamoto Yuki Etani Makoto Hirao Akira Miyama Gensuke Okamura Atsushi Goshima Taihei Miura Takuya Kurihara Yuji Fukuda Takashi Kanamoto Ken Nakata Seiji Okada Kosuke Ebina |
| author_facet | Kenji Takami Kazuki Okamoto Yuki Etani Makoto Hirao Akira Miyama Gensuke Okamura Atsushi Goshima Taihei Miura Takuya Kurihara Yuji Fukuda Takashi Kanamoto Ken Nakata Seiji Okada Kosuke Ebina |
| author_sort | Kenji Takami |
| collection | DOAJ |
| description | NF-κB is a transcription factor that is activated with aging. It plays a key role in the development of osteoporosis by promoting osteoclast differentiation and inhibiting osteoblast differentiation. In this study, we developed a small anti–NF-κB peptide called 6A-8R from a nuclear acidic protein (also known as macromolecular translocation inhibitor II, Zn2+-binding protein, or parathymosin) that inhibits transcriptional activity of NF-κB without altering its nuclear translocation and binding to DNA. Intraperitoneal injection of 6A-8R attenuated ovariectomy-induced osteoporosis in mice by inhibiting osteoclast differentiation, promoting osteoblast differentiation, and inhibiting sclerostin production by osteocytes in vivo with no apparent side effects. Conversely, in vitro, 6A-8R inhibited osteoclast differentiation by inhibiting NF-κB transcriptional activity, promoted osteoblast differentiation by promoting Smad1 phosphorylation, and inhibited sclerostin expression in osteocytes by inhibiting myocyte enhancer factors 2C and 2D. These findings suggest that 6A-8R has the potential to be an antiosteoporotic therapeutic agent with uncoupling properties. |
| first_indexed | 2024-03-11T12:05:47Z |
| format | Article |
| id | doaj.art-92566f0759554cdeb09b17a795bb8af6 |
| institution | Directory Open Access Journal |
| issn | 2379-3708 |
| language | English |
| last_indexed | 2024-03-11T12:05:47Z |
| publishDate | 2023-11-01 |
| publisher | American Society for Clinical investigation |
| record_format | Article |
| series | JCI Insight |
| spelling | doaj.art-92566f0759554cdeb09b17a795bb8af62023-11-07T16:26:27ZengAmerican Society for Clinical investigationJCI Insight2379-37082023-11-01822Anti–NF-κB peptide derived from nuclear acidic protein attenuates ovariectomy-induced osteoporosis in miceKenji TakamiKazuki OkamotoYuki EtaniMakoto HiraoAkira MiyamaGensuke OkamuraAtsushi GoshimaTaihei MiuraTakuya KuriharaYuji FukudaTakashi KanamotoKen NakataSeiji OkadaKosuke EbinaNF-κB is a transcription factor that is activated with aging. It plays a key role in the development of osteoporosis by promoting osteoclast differentiation and inhibiting osteoblast differentiation. In this study, we developed a small anti–NF-κB peptide called 6A-8R from a nuclear acidic protein (also known as macromolecular translocation inhibitor II, Zn2+-binding protein, or parathymosin) that inhibits transcriptional activity of NF-κB without altering its nuclear translocation and binding to DNA. Intraperitoneal injection of 6A-8R attenuated ovariectomy-induced osteoporosis in mice by inhibiting osteoclast differentiation, promoting osteoblast differentiation, and inhibiting sclerostin production by osteocytes in vivo with no apparent side effects. Conversely, in vitro, 6A-8R inhibited osteoclast differentiation by inhibiting NF-κB transcriptional activity, promoted osteoblast differentiation by promoting Smad1 phosphorylation, and inhibited sclerostin expression in osteocytes by inhibiting myocyte enhancer factors 2C and 2D. These findings suggest that 6A-8R has the potential to be an antiosteoporotic therapeutic agent with uncoupling properties.https://doi.org/10.1172/jci.insight.171962Bone biology |
| spellingShingle | Kenji Takami Kazuki Okamoto Yuki Etani Makoto Hirao Akira Miyama Gensuke Okamura Atsushi Goshima Taihei Miura Takuya Kurihara Yuji Fukuda Takashi Kanamoto Ken Nakata Seiji Okada Kosuke Ebina Anti–NF-κB peptide derived from nuclear acidic protein attenuates ovariectomy-induced osteoporosis in mice JCI Insight Bone biology |
| title | Anti–NF-κB peptide derived from nuclear acidic protein attenuates ovariectomy-induced osteoporosis in mice |
| title_full | Anti–NF-κB peptide derived from nuclear acidic protein attenuates ovariectomy-induced osteoporosis in mice |
| title_fullStr | Anti–NF-κB peptide derived from nuclear acidic protein attenuates ovariectomy-induced osteoporosis in mice |
| title_full_unstemmed | Anti–NF-κB peptide derived from nuclear acidic protein attenuates ovariectomy-induced osteoporosis in mice |
| title_short | Anti–NF-κB peptide derived from nuclear acidic protein attenuates ovariectomy-induced osteoporosis in mice |
| title_sort | anti nf κb peptide derived from nuclear acidic protein attenuates ovariectomy induced osteoporosis in mice |
| topic | Bone biology |
| url | https://doi.org/10.1172/jci.insight.171962 |
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