DataVXAdvanced SciencePaper
journal article·2025-10Open access

Osteoblast‐CD4 + CTL Crosstalk Mediated by SIRT1/DAAM2 Axis Prevents Age‐Related Bone Loss

Bin Yang, Guofu Zhang, Yizhou Zhu, Jingcheng Wang, Xinmin Feng, Wenyong Fei, Jihang Dai, Le Hu, Yi Zhang, Jun Cai, Binjia Ruan, Yue Jin, Fanhao Wei, Gang Lu, Dongan Wang, Jason Pui Yin Cheung, Graham Ka Hon Shea, Hao Chen, Kelvin Wai Kwok Yeung, Lei Wang, Yongxiang Wang

Advanced Science· Volume 12· Issue 39
Publisher pageOpen full text
Source abstract

Abstract

Abstract The dynamic production and clearance of senescent osteoblasts affects bone homeostasis and health. However, the relationship between senescent osteoblasts and the immune system remains unclear. Here, a landscape of the interaction between immune cells and osteoblasts through spatial analysis of the bone microenvironment is presented. Sirtuin 1 (SIRT1), a longevity gene, regulates bone mass maintenance through a mechanism involving osteoblast‐CD4 + cytotoxic T lymphocyte (CTL) crosstalk. In the osteoblastic niche, SIRT1 promotes the secretion of crucial chemokines, such as C‐C motif chemokine ligand 3 (CCL3), C‐C motif chemokine ligand 5 (CCL5), and C‐X‐C motif chemokine ligand 10 (CXCL10), by upregulating dishevelled‐associated activator of morphogenesis 2 (DAAM2) through the acetylation of enhancer of zeste homolog 2 (EZH2), activating and recruiting CD4 + CTLs that eliminate senescent osteoblasts in a major histocompatibility complex class II (MHC‐II)‐dependent manner, slowing the bone ageing process and ameliorating osteoporosis. DAAM2 serves as a pivotal downstream effector for SIRT1 to exert immune‐regulatory effects in the bone microenvironment; thus, targeting DAAM2 can treat osteoporosis by increasing CD4 + CTL responses. These results will facilitate the development of customised therapies targeting senescent osteoblasts to maintain bone health.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Neuroinflammation and Neurodegeneration Mechanisms · Immune cells in cancer · Cytomegalovirus and herpesvirus research

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Orthopaedics Northern Jiangsu People's Hospital Affiliated to Yangzhou University Yangzhou 225001 China

Northern Jiangsu People's Hospital Yangzhou 225001 China

Northern Jiangsu People's Hospital, Clinical Teaching Hospital of Medical School Nanjing University Yangzhou 225001 China

Department of Orthopaedics and Traumatology, School of Clinical Medicine, LKS Faculty of Medicine The University of Hong Kong Hong Kong SAR 999077 China

Department of Medical Research Center Northern Jiangsu People's Hospital Affiliated to Yangzhou University Yangzhou 225001 China

The Yangzhou School of Clinical Medicine of Dalian Medical University Yangzhou 225001 China

CUHK‐SDU Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences The Chinese University of Hong Kong Hong Kong 999077 China

Department of Biomedical Engineering City University of Hong Kong Hong Kong SAR 999077 China

Institute of Translational Medicine Medical College Yangzhou University Yangzhou 225000 China

Yangzhou Key Laboratory of Regenerative Medicine Yangzhou 225001 China

Funding

National Key Research and Development Program of China · National Natural Science Foundation of China

References (45)

Show source-provided references
1. 10.1038/s41586-020-2403-910.1038/s41586-020-2403-9 ↗
2. 10.1038/nrd.2017.11610.1038/nrd.2017.116 ↗
3. 10.1038/s41584-020-00533-710.1038/s41584-020-00533-7 ↗
4. 10.1152/physrev.00007.202210.1152/physrev.00007.2022 ↗
5. 10.1038/nm.438510.1038/nm.4385 ↗
6. 10.1038/s41556-023-01287-610.1038/s41556-023-01287-6 ↗
7. 10.1038/s41413-022-00204-110.1038/s41413-022-00204-1 ↗
8. 10.1056/NEJM19950202332050610.1056/NEJM199502023320506 ↗
9. 10.1016/j.ebiom.2023.10451410.1016/j.ebiom.2023.104514 ↗
10. 10.1016/j.cell.2023.02.03310.1016/j.cell.2023.02.033 ↗
11. 10.1016/j.immuni.2021.11.01510.1016/j.immuni.2021.11.015 ↗
12. 10.1126/scitranslmed.300316510.1126/scitranslmed.3003165 ↗
13. 10.1073/pnas.190788311610.1073/pnas.1907883116 ↗
14. 10.1016/j.devcel.2024.02.00810.1016/j.devcel.2024.02.008 ↗
15. 10.1111/acel.1330110.1111/acel.13301 ↗
16. 10.1007/s00198-016-3536-410.1007/s00198-016-3536-4 ↗
17. 10.1038/s41467-018-05187-410.1038/s41467-018-05187-4 ↗
18. 10.1038/s12276-022-00739-710.1038/s12276-022-00739-7 ↗
19. 10.1016/j.tem.2013.12.00110.1016/j.tem.2013.12.001 ↗
20. 10.1016/j.intimp.2021.10817510.1016/j.intimp.2021.108175 ↗
21. 10.1073/pnas.120214310910.1073/pnas.1202143109 ↗
22. 10.1016/j.cell.2020.05.01710.1016/j.cell.2020.05.017 ↗
23. 10.1111/febs.1446610.1111/febs.14466 ↗
24. 10.1016/j.coi.2008.03.00710.1016/j.coi.2008.03.007 ↗
25. 10.1016/j.neuron.2015.02.02410.1016/j.neuron.2015.02.024 ↗
26. 10.1038/s41588-018-0302-x10.1038/s41588-018-0302-x ↗
27. 10.1073/pnas.230411212010.1073/pnas.2304112120 ↗
28. 10.1038/s41467-019-10809-610.1038/s41467-019-10809-6 ↗
29. 10.1016/S2213-8587(21)00347-810.1016/S2213-8587(21)00347-8 ↗
30. 10.1136/annrheumdis-2020-21808910.1136/annrheumdis-2020-218089 ↗
31. 10.1038/s41580-020-00279-w10.1038/s41580-020-00279-w ↗
32. 10.1186/s40779-022-00426-810.1186/s40779-022-00426-8 ↗
33. 10.1111/j.1474-9726.2011.00669.x10.1111/j.1474-9726.2011.00669.x ↗
34. 10.1038/s41577-019-0178-810.1038/s41577-019-0178-8 ↗
35. 10.1038/s41392-023-01502-810.1038/s41392-023-01502-8 ↗
36. 10.1080/13697137.2020.175805710.1080/13697137.2020.1758057 ↗
37. 10.18632/aging.20363910.18632/aging.203639 ↗
38. 10.1007/s00018-010-0270-510.1007/s00018-010-0270-5 ↗
39. 10.4049/jimmunol.174.10.602310.4049/jimmunol.174.10.6023 ↗
40. 10.1172/JCI15180310.1172/JCI151803 ↗
41. 10.1093/nar/gkv23810.1093/nar/gkv238 ↗
42. 10.1002/hep.2965210.1002/hep.29652 ↗
43. 10.1002/advs.20210323010.1002/advs.202103230 ↗
44. 10.1016/j.yexcr.2015.09.00310.1016/j.yexcr.2015.09.003 ↗
45. 10.1038/s41596-023-00881-010.1038/s41596-023-00881-0 ↗