NEAT1 regulates BMSCs aging through disruption of FGF2 nuclear transport
Abstract Background The aging of bone marrow mesenchymal stem cells (BMSCs) impairs bone tissue regeneration, contributing to skeletal disorders. LncRNA NEAT1 is considered as a proliferative inhibitory role during cellular senescence, but the relevant mechanisms remain insufficient. This study aims...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-01-01
|
| Series: | Stem Cell Research & Therapy |
| Online Access: | https://doi.org/10.1186/s13287-025-04156-1 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832571956944175104 |
|---|---|
| author | Zifei Wang Wenyu Zhen Qing Wang Yuqiang Sun Siyu Jin Sensen Yu Xing Wu Wenhao Zhang Yulong Zhang Fei Xu Rui Wang Yuxuan Xie Wansu Sun Jianguang Xu Hengguo Zhang |
| author_facet | Zifei Wang Wenyu Zhen Qing Wang Yuqiang Sun Siyu Jin Sensen Yu Xing Wu Wenhao Zhang Yulong Zhang Fei Xu Rui Wang Yuxuan Xie Wansu Sun Jianguang Xu Hengguo Zhang |
| author_sort | Zifei Wang |
| collection | DOAJ |
| description | Abstract Background The aging of bone marrow mesenchymal stem cells (BMSCs) impairs bone tissue regeneration, contributing to skeletal disorders. LncRNA NEAT1 is considered as a proliferative inhibitory role during cellular senescence, but the relevant mechanisms remain insufficient. This study aims to elucidate how NEAT1 regulates mitotic proteins during BMSCs aging. Methods BMSCs were isolated from alveolar bone of human volunteers aged 26–33 (young) and 66–78 (aged). NEAT1 expression and distribution changes during aging process were observed using fluorescence in situ hybridization (FISH) in young (3 months) and aged (18 months) mice or human BMSCs. Subsequent RNA pulldown and proteomic analyses, along with single-cell analysis, immunofluorescence, RNA immunoprecipitation (RIP), and co-immunoprecipitation (Co-IP), were conducted to investigate that NEAT1 impairs the nuclear transport of mitotic FGF2 and contributes to BMSCs aging. Results We reveal that NEAT1 undergoes significant upregulated and shifts from nucleus to cytoplasm in bone marrow and BMSCs during aging process. In which, the expression correlates with nuclear DNA content during karyokinesis, suggesting a link to mitogenic factor. Within NEAT1 knockdown, hallmarks of cellular aging, including senescence-associated secretory phenotype (SASP), p16, and p21, were significantly downregulated. RNA pulldown and proteomic analyses further identify NEAT1 involved in osteoblast differentiation, mitotic cell cycle, and ribosome biogenesis, highlighting its role in maintaining BMSCs differentiation and proliferation. Notably, as an essential growth factor of BMSCs, Fibroblast Growth Factor 2 (FGF2) directly abundant binds to NEAT1 and the sites enriched with nuclear localization motifs. Importantly, NEAT1 decreased the interaction between FGF2 and Karyopherin Subunit Beta 1 (KPNB1), influencing the nuclear transport of mitogenic FGF2. Conclusions Our findings position NEAT1 as a critical regulator of mitogenic protein networks that govern BMSC aging. Targeting NEAT1 might offer novel therapeutic strategies to rejuvenate aged BMSCs. |
| format | Article |
| id | doaj-art-cc8a252fdf284c04a71b373b662029c0 |
| institution | Kabale University |
| issn | 1757-6512 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj-art-cc8a252fdf284c04a71b373b662029c02025-02-02T12:11:25ZengBMCStem Cell Research & Therapy1757-65122025-01-0116111310.1186/s13287-025-04156-1NEAT1 regulates BMSCs aging through disruption of FGF2 nuclear transportZifei Wang0Wenyu Zhen1Qing Wang2Yuqiang Sun3Siyu Jin4Sensen Yu5Xing Wu6Wenhao Zhang7Yulong Zhang8Fei Xu9Rui Wang10Yuxuan Xie11Wansu Sun12Jianguang Xu13Hengguo Zhang14College & Hospital of Stomatology, Key Laboratory of Oral Diseases Research of Anhui Province, Anhui Medical UniversityCollege & Hospital of Stomatology, Key Laboratory of Oral Diseases Research of Anhui Province, Anhui Medical UniversityCollege & Hospital of Stomatology, Key Laboratory of Oral Diseases Research of Anhui Province, Anhui Medical UniversityCollege & Hospital of Stomatology, Key Laboratory of Oral Diseases Research of Anhui Province, Anhui Medical UniversityCollege & Hospital of Stomatology, Key Laboratory of Oral Diseases Research of Anhui Province, Anhui Medical UniversityCollege & Hospital of Stomatology, Key Laboratory of Oral Diseases Research of Anhui Province, Anhui Medical UniversityCollege & Hospital of Stomatology, Key Laboratory of Oral Diseases Research of Anhui Province, Anhui Medical UniversityCollege & Hospital of Stomatology, Key Laboratory of Oral Diseases Research of Anhui Province, Anhui Medical UniversityCollege & Hospital of Stomatology, Key Laboratory of Oral Diseases Research of Anhui Province, Anhui Medical UniversityCollege & Hospital of Stomatology, Key Laboratory of Oral Diseases Research of Anhui Province, Anhui Medical UniversityCollege & Hospital of Stomatology, Key Laboratory of Oral Diseases Research of Anhui Province, Anhui Medical UniversityCollege & Hospital of Stomatology, Key Laboratory of Oral Diseases Research of Anhui Province, Anhui Medical UniversityDepartment of Stomatology, The First Affiliated Hospital of Anhui Medical UniversityCollege & Hospital of Stomatology, Key Laboratory of Oral Diseases Research of Anhui Province, Anhui Medical UniversityCollege & Hospital of Stomatology, Key Laboratory of Oral Diseases Research of Anhui Province, Anhui Medical UniversityAbstract Background The aging of bone marrow mesenchymal stem cells (BMSCs) impairs bone tissue regeneration, contributing to skeletal disorders. LncRNA NEAT1 is considered as a proliferative inhibitory role during cellular senescence, but the relevant mechanisms remain insufficient. This study aims to elucidate how NEAT1 regulates mitotic proteins during BMSCs aging. Methods BMSCs were isolated from alveolar bone of human volunteers aged 26–33 (young) and 66–78 (aged). NEAT1 expression and distribution changes during aging process were observed using fluorescence in situ hybridization (FISH) in young (3 months) and aged (18 months) mice or human BMSCs. Subsequent RNA pulldown and proteomic analyses, along with single-cell analysis, immunofluorescence, RNA immunoprecipitation (RIP), and co-immunoprecipitation (Co-IP), were conducted to investigate that NEAT1 impairs the nuclear transport of mitotic FGF2 and contributes to BMSCs aging. Results We reveal that NEAT1 undergoes significant upregulated and shifts from nucleus to cytoplasm in bone marrow and BMSCs during aging process. In which, the expression correlates with nuclear DNA content during karyokinesis, suggesting a link to mitogenic factor. Within NEAT1 knockdown, hallmarks of cellular aging, including senescence-associated secretory phenotype (SASP), p16, and p21, were significantly downregulated. RNA pulldown and proteomic analyses further identify NEAT1 involved in osteoblast differentiation, mitotic cell cycle, and ribosome biogenesis, highlighting its role in maintaining BMSCs differentiation and proliferation. Notably, as an essential growth factor of BMSCs, Fibroblast Growth Factor 2 (FGF2) directly abundant binds to NEAT1 and the sites enriched with nuclear localization motifs. Importantly, NEAT1 decreased the interaction between FGF2 and Karyopherin Subunit Beta 1 (KPNB1), influencing the nuclear transport of mitogenic FGF2. Conclusions Our findings position NEAT1 as a critical regulator of mitogenic protein networks that govern BMSC aging. Targeting NEAT1 might offer novel therapeutic strategies to rejuvenate aged BMSCs.https://doi.org/10.1186/s13287-025-04156-1 |
| spellingShingle | Zifei Wang Wenyu Zhen Qing Wang Yuqiang Sun Siyu Jin Sensen Yu Xing Wu Wenhao Zhang Yulong Zhang Fei Xu Rui Wang Yuxuan Xie Wansu Sun Jianguang Xu Hengguo Zhang NEAT1 regulates BMSCs aging through disruption of FGF2 nuclear transport Stem Cell Research & Therapy |
| title | NEAT1 regulates BMSCs aging through disruption of FGF2 nuclear transport |
| title_full | NEAT1 regulates BMSCs aging through disruption of FGF2 nuclear transport |
| title_fullStr | NEAT1 regulates BMSCs aging through disruption of FGF2 nuclear transport |
| title_full_unstemmed | NEAT1 regulates BMSCs aging through disruption of FGF2 nuclear transport |
| title_short | NEAT1 regulates BMSCs aging through disruption of FGF2 nuclear transport |
| title_sort | neat1 regulates bmscs aging through disruption of fgf2 nuclear transport |
| url | https://doi.org/10.1186/s13287-025-04156-1 |
| work_keys_str_mv | AT zifeiwang neat1regulatesbmscsagingthroughdisruptionoffgf2nucleartransport AT wenyuzhen neat1regulatesbmscsagingthroughdisruptionoffgf2nucleartransport AT qingwang neat1regulatesbmscsagingthroughdisruptionoffgf2nucleartransport AT yuqiangsun neat1regulatesbmscsagingthroughdisruptionoffgf2nucleartransport AT siyujin neat1regulatesbmscsagingthroughdisruptionoffgf2nucleartransport AT sensenyu neat1regulatesbmscsagingthroughdisruptionoffgf2nucleartransport AT xingwu neat1regulatesbmscsagingthroughdisruptionoffgf2nucleartransport AT wenhaozhang neat1regulatesbmscsagingthroughdisruptionoffgf2nucleartransport AT yulongzhang neat1regulatesbmscsagingthroughdisruptionoffgf2nucleartransport AT feixu neat1regulatesbmscsagingthroughdisruptionoffgf2nucleartransport AT ruiwang neat1regulatesbmscsagingthroughdisruptionoffgf2nucleartransport AT yuxuanxie neat1regulatesbmscsagingthroughdisruptionoffgf2nucleartransport AT wansusun neat1regulatesbmscsagingthroughdisruptionoffgf2nucleartransport AT jianguangxu neat1regulatesbmscsagingthroughdisruptionoffgf2nucleartransport AT hengguozhang neat1regulatesbmscsagingthroughdisruptionoffgf2nucleartransport |