Identification of NIBAN2‐Regulated RUNX2 Alternative Splicing Presents Novel Strategies for Antagonizing Osteoporosis
Abstract Osteoporosis is characterized by excessive bone resorption and/or defects in bone formation. Identification of factors promoting osteoblast differentiation may provide potential targets for osteoporosis therapy. Through integral analyses of multiple datasets, NIBAN2 is found to be tightly a...
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| Format: | Article |
| Language: | English |
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Wiley
2025-05-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202416536 |
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| author | Sheng Zhang Zhiqiang Yang Yuanlong Xie Yufeng Zhang Zhe Chen Xuan Lv Zhouming Deng Zan Huang Lin Cai Renxiong Wei |
| author_facet | Sheng Zhang Zhiqiang Yang Yuanlong Xie Yufeng Zhang Zhe Chen Xuan Lv Zhouming Deng Zan Huang Lin Cai Renxiong Wei |
| author_sort | Sheng Zhang |
| collection | DOAJ |
| description | Abstract Osteoporosis is characterized by excessive bone resorption and/or defects in bone formation. Identification of factors promoting osteoblast differentiation may provide potential targets for osteoporosis therapy. Through integral analyses of multiple datasets, NIBAN2 is found to be tightly associated with bone formation and osteoporosis. Indeed, NIBAN2 promotes osteoblast differentiation, and conditional Niban2 knockout in osteoblasts caused bone loss and insufficient mineralization. Mechanistically, NIBAN2 interacts with the HNRNPU‐cored spliceosome complex and alters its components to regulate the alternative splicing of RUNX2, which ultimately cause an increase in functional RUNX2 (nuclear localization sequence complete) but a decrease in dysfunctional RUNX2 (exon 6 exclusive) to reinforce osteoblast differentiation. Most importantly, NIBAN2 expression level negatively correlates with RUNX2 spliced isoforms and bone loss in osteoporosis patients. NIBAN2 overexpression rescues bone loss in ovariectomized mice. Thus, this research identifies NIBAN2‐regulated RUNX2 alternative splicing as a potential mechanism of osteoblast differentiation that may present strategies for antagonizing osteoporosis. |
| format | Article |
| id | doaj-art-aec0d596322b493aa2d5be542b4af805 |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-aec0d596322b493aa2d5be542b4af8052025-08-20T03:48:47ZengWileyAdvanced Science2198-38442025-05-011217n/an/a10.1002/advs.202416536Identification of NIBAN2‐Regulated RUNX2 Alternative Splicing Presents Novel Strategies for Antagonizing OsteoporosisSheng Zhang0Zhiqiang Yang1Yuanlong Xie2Yufeng Zhang3Zhe Chen4Xuan Lv5Zhouming Deng6Zan Huang7Lin Cai8Renxiong Wei9Department of Spine Surgery and Musculoskeletal Tumor Zhongnan Hospital of Wuhan University No. 163 Donghu Road Wuhan Hubei 430071 P. R. ChinaDepartment of Spine Surgery and Musculoskeletal Tumor Zhongnan Hospital of Wuhan University No. 163 Donghu Road Wuhan Hubei 430071 P. R. ChinaDepartment of Spine Surgery and Musculoskeletal Tumor Zhongnan Hospital of Wuhan University No. 163 Donghu Road Wuhan Hubei 430071 P. R. ChinaDepartment of Orthopedics The Second Hospital of Tianjin Medical University No.23 Pingjiang Road Tianjin 300211 ChinaDepartment of Spine Surgery and Musculoskeletal Tumor Zhongnan Hospital of Wuhan University No. 163 Donghu Road Wuhan Hubei 430071 P. R. ChinaDepartment of Spine Surgery and Musculoskeletal Tumor Zhongnan Hospital of Wuhan University No. 163 Donghu Road Wuhan Hubei 430071 P. R. ChinaDepartment of Spine Surgery and Musculoskeletal Tumor Zhongnan Hospital of Wuhan University No. 163 Donghu Road Wuhan Hubei 430071 P. R. ChinaCollege of Life Sciences Key Laboratory of Cell Hemostasis of Hubei Province Wuhan University No. 299 Bayi Road Wuhan Hubei 430072 P. R. ChinaDepartment of Spine Surgery and Musculoskeletal Tumor Zhongnan Hospital of Wuhan University No. 163 Donghu Road Wuhan Hubei 430071 P. R. ChinaDepartment of Spine Surgery and Musculoskeletal Tumor Zhongnan Hospital of Wuhan University No. 163 Donghu Road Wuhan Hubei 430071 P. R. ChinaAbstract Osteoporosis is characterized by excessive bone resorption and/or defects in bone formation. Identification of factors promoting osteoblast differentiation may provide potential targets for osteoporosis therapy. Through integral analyses of multiple datasets, NIBAN2 is found to be tightly associated with bone formation and osteoporosis. Indeed, NIBAN2 promotes osteoblast differentiation, and conditional Niban2 knockout in osteoblasts caused bone loss and insufficient mineralization. Mechanistically, NIBAN2 interacts with the HNRNPU‐cored spliceosome complex and alters its components to regulate the alternative splicing of RUNX2, which ultimately cause an increase in functional RUNX2 (nuclear localization sequence complete) but a decrease in dysfunctional RUNX2 (exon 6 exclusive) to reinforce osteoblast differentiation. Most importantly, NIBAN2 expression level negatively correlates with RUNX2 spliced isoforms and bone loss in osteoporosis patients. NIBAN2 overexpression rescues bone loss in ovariectomized mice. Thus, this research identifies NIBAN2‐regulated RUNX2 alternative splicing as a potential mechanism of osteoblast differentiation that may present strategies for antagonizing osteoporosis.https://doi.org/10.1002/advs.202416536alternative splicingbone mineralizationosteoblast differentiationosteoporosisRUNX2 |
| spellingShingle | Sheng Zhang Zhiqiang Yang Yuanlong Xie Yufeng Zhang Zhe Chen Xuan Lv Zhouming Deng Zan Huang Lin Cai Renxiong Wei Identification of NIBAN2‐Regulated RUNX2 Alternative Splicing Presents Novel Strategies for Antagonizing Osteoporosis Advanced Science alternative splicing bone mineralization osteoblast differentiation osteoporosis RUNX2 |
| title | Identification of NIBAN2‐Regulated RUNX2 Alternative Splicing Presents Novel Strategies for Antagonizing Osteoporosis |
| title_full | Identification of NIBAN2‐Regulated RUNX2 Alternative Splicing Presents Novel Strategies for Antagonizing Osteoporosis |
| title_fullStr | Identification of NIBAN2‐Regulated RUNX2 Alternative Splicing Presents Novel Strategies for Antagonizing Osteoporosis |
| title_full_unstemmed | Identification of NIBAN2‐Regulated RUNX2 Alternative Splicing Presents Novel Strategies for Antagonizing Osteoporosis |
| title_short | Identification of NIBAN2‐Regulated RUNX2 Alternative Splicing Presents Novel Strategies for Antagonizing Osteoporosis |
| title_sort | identification of niban2 regulated runx2 alternative splicing presents novel strategies for antagonizing osteoporosis |
| topic | alternative splicing bone mineralization osteoblast differentiation osteoporosis RUNX2 |
| url | https://doi.org/10.1002/advs.202416536 |
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