Ni-MOF engineered system targeting macrophage aurora A kinase for bone loss prevention through PD-L1 activation
Postmenopausal bone loss due to estrogen deficiency necessitates effective therapeutic strategies. Our study explores targeting macrophage Aurora A kinase to mitigate bone loss. Aurora A kinase phosphorylation is observed being increased in bone marrow-derived macrophages (BMDMs) from ovariectomy (O...
| Main Authors: | , , , , , , , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2025
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| Subjects: | |
| Online Access: | https://hdl.handle.net/10356/182775 |
| _version_ | 1826114751041634304 |
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| author | Zhang, Wenqian Zhang, Shengming He, Minghao Hu, Weixian Han, Wenhao Zha, Kangkang Feng, Qian Liu, Guohui Zhao, Yanli Mi, Bobin |
| author2 | School of Chemistry, Chemical Engineering and Biotechnology |
| author_facet | School of Chemistry, Chemical Engineering and Biotechnology Zhang, Wenqian Zhang, Shengming He, Minghao Hu, Weixian Han, Wenhao Zha, Kangkang Feng, Qian Liu, Guohui Zhao, Yanli Mi, Bobin |
| author_sort | Zhang, Wenqian |
| collection | NTU |
| description | Postmenopausal bone loss due to estrogen deficiency necessitates effective therapeutic strategies. Our study explores targeting macrophage Aurora A kinase to mitigate bone loss. Aurora A kinase phosphorylation is observed being increased in bone marrow-derived macrophages (BMDMs) from ovariectomy (OVX) mice, along with a reduction in programmed death-ligand 1 (PD-L1) expression. Detailed analysis reveals that PD-L1 plays an immunomodulatory role by lowering the ratio of T helper 17 cells and regulatory T cells. The metabolic shift toward glycolysis through transcriptome sequencing, induced by Aurora A kinase inhibition, is essential for PD-L1 expression in BMDMs. The interaction between Aurora A kinase and cytochrome C oxidase subunit 5B is found to enhance PD-L1 expression. To apply these findings therapeutically, a multifunctional system is developed using a Nickel-metal organic framework combined with bisphosphonate and MLN8237 (BP@Ni-MOF/MLN8237). This system targets bone tissues through bisphosphonate and effectively delivers MLN8237 to macrophages, promoting PD-L1 expression for a favorable immune environment. Moreover, this system exhibits an obvious angiogenic effect. The present study highlights the crucial roles of macrophage Aurora A kinase and PD-L1 in maintaining bone homeostasis as well as the angiogenesis effect by Ni-MOF engineered system, presenting a promising therapeutic approach to prevent postmenopausal bone loss. |
| first_indexed | 2025-03-09T11:12:16Z |
| format | Journal Article |
| id | ntu-10356/182775 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2025-03-09T11:12:16Z |
| publishDate | 2025 |
| record_format | dspace |
| spelling | ntu-10356/1827752025-02-25T01:49:29Z Ni-MOF engineered system targeting macrophage aurora A kinase for bone loss prevention through PD-L1 activation Zhang, Wenqian Zhang, Shengming He, Minghao Hu, Weixian Han, Wenhao Zha, Kangkang Feng, Qian Liu, Guohui Zhao, Yanli Mi, Bobin School of Chemistry, Chemical Engineering and Biotechnology Medicine, Health and Life Sciences Angiogenesis Aurora A kinase Postmenopausal bone loss due to estrogen deficiency necessitates effective therapeutic strategies. Our study explores targeting macrophage Aurora A kinase to mitigate bone loss. Aurora A kinase phosphorylation is observed being increased in bone marrow-derived macrophages (BMDMs) from ovariectomy (OVX) mice, along with a reduction in programmed death-ligand 1 (PD-L1) expression. Detailed analysis reveals that PD-L1 plays an immunomodulatory role by lowering the ratio of T helper 17 cells and regulatory T cells. The metabolic shift toward glycolysis through transcriptome sequencing, induced by Aurora A kinase inhibition, is essential for PD-L1 expression in BMDMs. The interaction between Aurora A kinase and cytochrome C oxidase subunit 5B is found to enhance PD-L1 expression. To apply these findings therapeutically, a multifunctional system is developed using a Nickel-metal organic framework combined with bisphosphonate and MLN8237 (BP@Ni-MOF/MLN8237). This system targets bone tissues through bisphosphonate and effectively delivers MLN8237 to macrophages, promoting PD-L1 expression for a favorable immune environment. Moreover, this system exhibits an obvious angiogenic effect. The present study highlights the crucial roles of macrophage Aurora A kinase and PD-L1 in maintaining bone homeostasis as well as the angiogenesis effect by Ni-MOF engineered system, presenting a promising therapeutic approach to prevent postmenopausal bone loss. This work was supported by the National Science Foundation of China (82372406), the National Key Research & Development Program of China (2021YFA1101503), and the Wuhan Science and Technology Bureau (2022020801020464). 2025-02-25T01:49:29Z 2025-02-25T01:49:29Z 2025 Journal Article Zhang, W., Zhang, S., He, M., Hu, W., Han, W., Zha, K., Feng, Q., Liu, G., Zhao, Y. & Mi, B. (2025). Ni-MOF engineered system targeting macrophage aurora A kinase for bone loss prevention through PD-L1 activation. Advanced Functional Materials, 35(3), 2413913-. https://dx.doi.org/10.1002/adfm.202413913 1616-301X https://hdl.handle.net/10356/182775 10.1002/adfm.202413913 2-s2.0-85208025408 3 35 2413913 en Advanced Functional Materials © 2024 Wiley-VCH GmbH. All rights reserved. |
| spellingShingle | Medicine, Health and Life Sciences Angiogenesis Aurora A kinase Zhang, Wenqian Zhang, Shengming He, Minghao Hu, Weixian Han, Wenhao Zha, Kangkang Feng, Qian Liu, Guohui Zhao, Yanli Mi, Bobin Ni-MOF engineered system targeting macrophage aurora A kinase for bone loss prevention through PD-L1 activation |
| title | Ni-MOF engineered system targeting macrophage aurora A kinase for bone loss prevention through PD-L1 activation |
| title_full | Ni-MOF engineered system targeting macrophage aurora A kinase for bone loss prevention through PD-L1 activation |
| title_fullStr | Ni-MOF engineered system targeting macrophage aurora A kinase for bone loss prevention through PD-L1 activation |
| title_full_unstemmed | Ni-MOF engineered system targeting macrophage aurora A kinase for bone loss prevention through PD-L1 activation |
| title_short | Ni-MOF engineered system targeting macrophage aurora A kinase for bone loss prevention through PD-L1 activation |
| title_sort | ni mof engineered system targeting macrophage aurora a kinase for bone loss prevention through pd l1 activation |
| topic | Medicine, Health and Life Sciences Angiogenesis Aurora A kinase |
| url | https://hdl.handle.net/10356/182775 |
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