Psychological stress disturbs bone metabolism via miR-335-3p/Fos signaling in osteoclast
It has been well validated that chronic psychological stress leads to bone loss, but the underlying mechanism remains unclarified. In this study, we established and analyzed the chronic unpredictable mild stress (CUMS) mice to investigate the miRNA-related pathogenic mechanism involved in psychologi...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2025-01-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/95944 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841554349695696896 |
|---|---|
| author | Jiayao Zhang Juan Li Jiehong Huang Xuerui Xiang Ruoyu Li Yun Zhai Shuxian Lin Weicai Liu |
| author_facet | Jiayao Zhang Juan Li Jiehong Huang Xuerui Xiang Ruoyu Li Yun Zhai Shuxian Lin Weicai Liu |
| author_sort | Jiayao Zhang |
| collection | DOAJ |
| description | It has been well validated that chronic psychological stress leads to bone loss, but the underlying mechanism remains unclarified. In this study, we established and analyzed the chronic unpredictable mild stress (CUMS) mice to investigate the miRNA-related pathogenic mechanism involved in psychological stress-induced osteoporosis. Our result found that these CUMS mice exhibited osteoporosis phenotype that is mainly attributed to the abnormal activities of osteoclasts. Subsequently, miRNA sequencing and other analysis showed that miR-335-3p, which is normally highly expressed in the brain, was significantly downregulated in the nucleus ambiguous, serum, and bone of the CUMS mice. Additionally, in vitro studies detected that miR-335-3p is important for osteoclast differentiation, with its direct targeting site in Fos. Further studies demonstrated FOS was upregulated in CUMS osteoclast, and the inhibition of FOS suppressed the accelerated osteoclastic differentiation, as well as the expression of osteoclastic genes, such as Nfatc1, Acp5, and Mmp9, in miR-335-3p-restrained osteoclasts. In conclusion, this work indicated that psychological stress may downregulate the miR-335-3p expression, which resulted in the accumulation of FOS and the upregulation of NFACT1 signaling pathway in osteoclasts, leading to its accelerated differentiation and abnormal activity. These results decipher a previously unrecognized paradigm that miRNA can act as a link between psychological stress and bone metabolism. |
| format | Article |
| id | doaj-art-a9bf1cc5859c4beba08570047f747167 |
| institution | Kabale University |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj-art-a9bf1cc5859c4beba08570047f7471672025-01-08T14:12:16ZengeLife Sciences Publications LtdeLife2050-084X2025-01-011310.7554/eLife.95944Psychological stress disturbs bone metabolism via miR-335-3p/Fos signaling in osteoclastJiayao Zhang0https://orcid.org/0000-0003-2029-6665Juan Li1Jiehong Huang2Xuerui Xiang3Ruoyu Li4Yun Zhai5Shuxian Lin6https://orcid.org/0000-0001-6944-5604Weicai Liu7https://orcid.org/0000-0002-7709-6771Shanghai Engineering Research Center of Tooth Restoration and Regeneration & Tongji Research Institute of Stomatology & Department of Prosthodontics, Shanghai Tongji Stomatological Hospital and Dental School, Tongji University, Shanghai, ChinaShanghai Engineering Research Center of Tooth Restoration and Regeneration & Tongji Research Institute of Stomatology & Department of Prosthodontics, Shanghai Tongji Stomatological Hospital and Dental School, Tongji University, Shanghai, ChinaDepartment of Neurology and Neurological Rehabilitation, Shanghai Disabled Persons' Federation Key Laboratory of Intelligent Rehabilitation Assistive Devices and Technologies, Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), School of Medicine, Tongji University, Shanghai, ChinaDepartment of Neurology and Neurological Rehabilitation, Shanghai Disabled Persons' Federation Key Laboratory of Intelligent Rehabilitation Assistive Devices and Technologies, Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), School of Medicine, Tongji University, Shanghai, ChinaDepartment of Neurology and Neurological Rehabilitation, Shanghai Disabled Persons' Federation Key Laboratory of Intelligent Rehabilitation Assistive Devices and Technologies, Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), School of Medicine, Tongji University, Shanghai, ChinaShanghai Engineering Research Center of Tooth Restoration and Regeneration & Tongji Research Institute of Stomatology & Department of Prosthodontics, Shanghai Tongji Stomatological Hospital and Dental School, Tongji University, Shanghai, ChinaShanghai Engineering Research Center of Tooth Restoration and Regeneration & Tongji Research Institute of Stomatology & Department of Prosthodontics, Shanghai Tongji Stomatological Hospital and Dental School, Tongji University, Shanghai, ChinaShanghai Engineering Research Center of Tooth Restoration and Regeneration & Tongji Research Institute of Stomatology & Department of Prosthodontics, Shanghai Tongji Stomatological Hospital and Dental School, Tongji University, Shanghai, ChinaIt has been well validated that chronic psychological stress leads to bone loss, but the underlying mechanism remains unclarified. In this study, we established and analyzed the chronic unpredictable mild stress (CUMS) mice to investigate the miRNA-related pathogenic mechanism involved in psychological stress-induced osteoporosis. Our result found that these CUMS mice exhibited osteoporosis phenotype that is mainly attributed to the abnormal activities of osteoclasts. Subsequently, miRNA sequencing and other analysis showed that miR-335-3p, which is normally highly expressed in the brain, was significantly downregulated in the nucleus ambiguous, serum, and bone of the CUMS mice. Additionally, in vitro studies detected that miR-335-3p is important for osteoclast differentiation, with its direct targeting site in Fos. Further studies demonstrated FOS was upregulated in CUMS osteoclast, and the inhibition of FOS suppressed the accelerated osteoclastic differentiation, as well as the expression of osteoclastic genes, such as Nfatc1, Acp5, and Mmp9, in miR-335-3p-restrained osteoclasts. In conclusion, this work indicated that psychological stress may downregulate the miR-335-3p expression, which resulted in the accumulation of FOS and the upregulation of NFACT1 signaling pathway in osteoclasts, leading to its accelerated differentiation and abnormal activity. These results decipher a previously unrecognized paradigm that miRNA can act as a link between psychological stress and bone metabolism.https://elifesciences.org/articles/95944psychological stressosteoporosismiR-335-3posteoclast |
| spellingShingle | Jiayao Zhang Juan Li Jiehong Huang Xuerui Xiang Ruoyu Li Yun Zhai Shuxian Lin Weicai Liu Psychological stress disturbs bone metabolism via miR-335-3p/Fos signaling in osteoclast eLife psychological stress osteoporosis miR-335-3p osteoclast |
| title | Psychological stress disturbs bone metabolism via miR-335-3p/Fos signaling in osteoclast |
| title_full | Psychological stress disturbs bone metabolism via miR-335-3p/Fos signaling in osteoclast |
| title_fullStr | Psychological stress disturbs bone metabolism via miR-335-3p/Fos signaling in osteoclast |
| title_full_unstemmed | Psychological stress disturbs bone metabolism via miR-335-3p/Fos signaling in osteoclast |
| title_short | Psychological stress disturbs bone metabolism via miR-335-3p/Fos signaling in osteoclast |
| title_sort | psychological stress disturbs bone metabolism via mir 335 3p fos signaling in osteoclast |
| topic | psychological stress osteoporosis miR-335-3p osteoclast |
| url | https://elifesciences.org/articles/95944 |
| work_keys_str_mv | AT jiayaozhang psychologicalstressdisturbsbonemetabolismviamir3353pfossignalinginosteoclast AT juanli psychologicalstressdisturbsbonemetabolismviamir3353pfossignalinginosteoclast AT jiehonghuang psychologicalstressdisturbsbonemetabolismviamir3353pfossignalinginosteoclast AT xueruixiang psychologicalstressdisturbsbonemetabolismviamir3353pfossignalinginosteoclast AT ruoyuli psychologicalstressdisturbsbonemetabolismviamir3353pfossignalinginosteoclast AT yunzhai psychologicalstressdisturbsbonemetabolismviamir3353pfossignalinginosteoclast AT shuxianlin psychologicalstressdisturbsbonemetabolismviamir3353pfossignalinginosteoclast AT weicailiu psychologicalstressdisturbsbonemetabolismviamir3353pfossignalinginosteoclast |