Targeting Bacteria‐Induced Ferroptosis of Bone Marrow Mesenchymal Stem Cells to Promote the Repair of Infected Bone Defects
Source abstract
Abstract
Abstract The specific mechanisms underlying bacteria‐triggered cell death and osteogenic dysfunction in host bone marrow mesenchymal stem cells (BMSCs) remain unclear, posing a significant challenge to the repair of infected bone defects. This study identifies ferroptosis as the predominant cause of BMSCs death in the infected bone microenvironment. Mechanistically, the bacteria‐induced activation of the innate immune response in BMSCs leads to upregulation and phosphorylation of interferon regulatory factor 7 (IRF7), thus facilitating IRF7‐dependent ferroptosis of BMSCs through the transcriptional upregulation of acyl‐coenzyme A synthetase long‐chain family member 4 (ACSL4). Moreover, it is found that intervening in ferroptosis can partially rescue cell injuries and osteogenic dysfunction. Based on these findings, a hydrogel composite 3D‐printed scaffold is designed with reactive oxygen species (ROS)‐responsive release of antibacterial quaternized chitosan and sustained delivery of the ferroptosis inhibitor Ferrostatin‐1 (Fer‐1), capable of eradicating pathogens and promoting bone regeneration in a rat model of infected bone defects. Together, this study suggests that ferroptosis of BMSCs is a promising therapeutic target for infected bone defect repair.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Cancer-related molecular mechanisms research · Ferroptosis and cancer prognosis · MicroRNA in disease regulation
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Shanghai Key Laboratory of Orthopaedic Implants Department of Orthopaedic Surgery Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200011 P. R. China
Department of Orthopedics The First Affiliated Hospital Zhejiang University School of Medicine 79 Qingchun Rd Hangzhou 310003 P. R. China
Department of Orthopaedic Surgery The First Affiliated Hospital of Soochow University No. 899 Ping Hai Road Suzhou Jiangsu 215006 P. R. China
Department of Orthopaedic Surgery Xuzhou Central Hospital Xuzhou Clinical School of Xuzhou Medical University 199 Jiefang South Road Xuzhou 221009 P. R. China
Shanghai Institute of Precision Medicine Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200125 P. R. China
Jiangxi Key Laboratory of Nanobiomaterials & School of Materials Science and Engineering East China Jiaotong University Nanchang 330000 P. R. China
State Key Laboratory of Systems Medicine for Cancer Renji‐Med X Clinical Stem Cell Research Center Ren Ji Hospital Shanghai Jiao Tong University School of Medicine 160 Pujian Road Shanghai 200127 P. R. China
Funding
National Natural Science Foundation of China · China Postdoctoral Science Foundation
References (89)
Show source-provided references
1. 10.1038/s41572-022-00396-010.1038/s41572-022-00396-0 ↗
2. 10.1038/s41572-021-00289-810.1038/s41572-021-00289-8 ↗
3. 10.1086/31870410.1086/318704 ↗
4. 10.1016/j.rbo.2015.09.01010.1016/j.rbo.2015.09.010 ↗
5. 10.1016/j.cmi.2018.03.04010.1016/j.cmi.2018.03.040 ↗
6. 10.1016/S0020-1383(18)30310-310.1016/S0020-1383(18)30310-3 ↗
7. 10.1016/j.injury.2016.09.01910.1016/j.injury.2016.09.019 ↗
8. 10.5435/JAAOS-D-20-0093910.5435/JAAOS-D-20-00939 ↗
9. 10.1016/j.arth.2020.07.08110.1016/j.arth.2020.07.081 ↗
10. 10.1302/0301-620X.102B12.BJJ-2020-0792.R110.1302/0301-620X.102B12.BJJ-2020-0792.R1 ↗
11. 10.1038/s41467-018-03124-z10.1038/s41467-018-03124-z ↗
12. 10.1002/stem.194510.1002/stem.1945 ↗
13. 10.1038/s41580-020-00279-w10.1038/s41580-020-00279-w ↗
14. 10.1016/j.stem.2022.10.00210.1016/j.stem.2022.10.002 ↗
15. 10.1016/j.chom.2013.05.00310.1016/j.chom.2013.05.003 ↗
16. 10.3389/fcimb.2015.0008510.3389/fcimb.2015.00085 ↗
17. 10.1128/IAI.00152-1610.1128/IAI.00152-16 ↗
18. 10.1038/nrrheum.2012.110.1038/nrrheum.2012.1 ↗
19. 10.1371/journal.pone.004058610.1371/journal.pone.0040586 ↗
20. 10.1371/journal.pone.001874810.1371/journal.pone.0018748 ↗
21. 10.1016/j.bone.2016.02.02010.1016/j.bone.2016.02.020 ↗
22. 10.1002/jbmr.305510.1002/jbmr.3055 ↗
23. 10.1016/j.cmi.2016.06.02010.1016/j.cmi.2016.06.020 ↗
24. 10.1111/cmi.1331710.1111/cmi.13317 ↗
25. 10.1038/s41580-020-00324-810.1038/s41580-020-00324-8 ↗
26. 10.1038/s41413-023-00247-y10.1038/s41413-023-00247-y ↗
27. 10.1084/jem.2018177610.1084/jem.20181776 ↗
28. 10.1038/s41467-023-37148-x10.1038/s41467-023-37148-x ↗
29. 10.1172/JCI9949010.1172/JCI99490 ↗
30. 10.1016/j.cmi.2019.08.00610.1016/j.cmi.2019.08.006 ↗
31. 10.3390/ijms1703033410.3390/ijms17030334 ↗
32. 10.1097/BOT.000000000000111510.1097/BOT.0000000000001115 ↗
33. 10.1016/j.jot.2020.11.00810.1016/j.jot.2020.11.008 ↗
34. 10.1016/j.actbio.2018.08.01510.1016/j.actbio.2018.08.015 ↗
35. 10.1002/adhm.20220134910.1002/adhm.202201349 ↗
36. 10.1177/204173142096579710.1177/2041731420965797 ↗
37. 10.1016/j.bioactmat.2023.07.00410.1016/j.bioactmat.2023.07.004 ↗
38. 10.1126/sciadv.adf864510.1126/sciadv.adf8645 ↗
39. 10.1016/j.jot.2021.11.00510.1016/j.jot.2021.11.005 ↗
40. 10.1038/ncb353010.1038/ncb3530 ↗
41. 10.1016/j.expneurol.2021.11382810.1016/j.expneurol.2021.113828 ↗
42. 10.1186/s12974-022-02602-y10.1186/s12974-022-02602-y ↗
43. 10.1016/j.redox.2023.10285710.1016/j.redox.2023.102857 ↗
44. 10.1016/j.immuni.2011.05.00610.1016/j.immuni.2011.05.006 ↗
45. 10.1016/j.mam.2022.10114310.1016/j.mam.2022.101143 ↗
46. 10.1038/s41422-020-00441-110.1038/s41422-020-00441-1 ↗
47. 10.1038/s41556-021-00818-310.1038/s41556-021-00818-3 ↗
48. 10.1016/j.ccell.2022.02.00310.1016/j.ccell.2022.02.003 ↗
49. 10.1016/j.redox.2022.10226210.1016/j.redox.2022.102262 ↗
50. 10.1128/mBio.00141-1110.1128/mBio.00141-11 ↗
51. 10.1016/j.carbpol.2010.02.00810.1016/j.carbpol.2010.02.008 ↗
52. 10.1016/j.biomaterials.2011.09.08410.1016/j.biomaterials.2011.09.084 ↗
53. 10.1016/j.jot.2021.07.00610.1016/j.jot.2021.07.006 ↗
54. 10.1016/j.cej.2022.13807710.1016/j.cej.2022.138077 ↗
55. 10.1099/mic.0.063016-010.1099/mic.0.063016-0 ↗
56. 10.1152/ajpcell.00449.200410.1152/ajpcell.00449.2004 ↗
57. 10.1038/nrmicro226510.1038/nrmicro2265 ↗
58. 10.1038/s41413-019-0061-z10.1038/s41413-019-0061-z ↗
59. 10.1038/s41564-022-01278-710.1038/s41564-022-01278-7 ↗
60. 10.1038/s41586-022-04825-810.1038/s41586-022-04825-8 ↗
61. 10.3389/fimmu.2023.119084110.3389/fimmu.2023.1190841 ↗
62. 10.1007/s00018-020-03656-y10.1007/s00018-020-03656-y ↗
63. 10.1016/j.smim.2003.10.00310.1016/j.smim.2003.10.003 ↗
64. 10.1021/acs.jmedchem.0c0088410.1021/acs.jmedchem.0c00884 ↗
65. 10.1042/BST2016025910.1042/BST20160259 ↗
66. 10.1016/j.addr.2007.11.00510.1016/j.addr.2007.11.005 ↗
67. 10.1038/s41467-022-34602-010.1038/s41467-022-34602-0 ↗
68. 10.1038/s41598-020-75108-310.1038/s41598-020-75108-3 ↗
69. 10.1126/scitranslmed.aaf115610.1126/scitranslmed.aaf1156 ↗
70. 10.3389/fimmu.2017.0054210.3389/fimmu.2017.00542 ↗
71. 10.1128/mBio.01675-1610.1128/mBio.01675-16 ↗
72. 10.3389/fimmu.2022.84285810.3389/fimmu.2022.842858 ↗
73. 10.1016/j.redox.2021.10197110.1016/j.redox.2021.101971 ↗
74. 10.1038/s41413-022-00198-w10.1038/s41413-022-00198-w ↗
75. 10.1016/j.bcp.2010.07.01410.1016/j.bcp.2010.07.014 ↗
76. 10.1007/s00018-016-2223-010.1007/s00018-016-2223-0 ↗
77. 10.1002/adhm.20230012210.1002/adhm.202300122 ↗
78. 10.1186/s12951-020-00594-610.1186/s12951-020-00594-6 ↗
79. 10.1021/acsbiomaterials.0c0119010.1021/acsbiomaterials.0c01190 ↗
80. 10.22203/eCM.v042a2210.22203/eCM.v042a22 ↗
81. 10.1172/JCI8951110.1172/JCI89511 ↗
82. 10.2147/IJN.S25774110.2147/IJN.S257741 ↗
83. 10.1111/cpr.1347610.1111/cpr.13476 ↗
84. 10.1016/j.bioactmat.2022.03.02910.1016/j.bioactmat.2022.03.029 ↗
85. 10.1016/j.actbio.2012.03.01310.1016/j.actbio.2012.03.013 ↗
86. 10.1016/j.cej.2022.13807710.1016/j.cej.2022.138077 ↗
87. 10.1016/j.bioactmat.2020.10.02210.1016/j.bioactmat.2020.10.022 ↗
88. 10.1016/j.nantod.2022.10168310.1016/j.nantod.2022.101683 ↗
89. 10.1016/j.ijbiomac.2023.12639110.1016/j.ijbiomac.2023.126391 ↗