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已发表论文
COMMD1 通过 NF-κB 通路调节马尔尼菲篮状菌诱导的骨髓炎中的破骨细胞分化
Authors Zhang Y, Yang F, Zhao W , Wei R , Zeng G, Zong S
Received 4 June 2025
Accepted for publication 24 October 2025
Published 21 November 2025 Volume 2025:18 Pages 6079—6092
DOI https://doi.org/10.2147/IDR.S544816
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Professor Héctor Mora-Montes
Yi Zhang,1,* Fayun Yang,1,* Weilun Zhao,2 Rufei Wei,3 Gaofeng Zeng,3 Shaohui Zong1,4
1Department of Spine Osteopathia, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China; 2Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry, Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China; 3School of Public Health, Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China; 4Wuming Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Shaohui Zong, Department of Spine Osteopathia, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Qingxiu District, Nanning, Guangxi, 530021, People’s Republic of China, Email zongshaohui@gxmu.edu.cn Gaofeng Zeng, School of Public Health, Guangxi Medical University, No. 22, Shuangyong Road, Qingxiu District, Nanning, Guangxi, 530021, People’s Republic of China, Email zenggaofeng@gxmu.edu.cn
Purpose: This study investigated the role of copper metabolism MURR1 domain-containing 1 (COMMD1) in Talaromyces marneffei (TM)-induced osteomyelitis (OM) and its regulation of osteoclast differentiation via the NF-κB pathway.
Methods: A murine TM infection model was used to assess bone destruction and osteoclast activity via micro-CT, histological analysis, biomechanical testing, qPCR, and Western blot. RNA sequencing was performed to analyze differentially expressed genes. Functional validation was conducted using COMMD1 conditional knockout (cKO) mice and bone marrow-derived monocytes macrophages (BMMs). The NF-κB inhibitor JSH-23 was used to verify pathway dependency.
Results: TM infection significantly upregulated inflammatory cytokines (IL-10, IL-17, TNF-α) and induced severe bone structural damage, characterized by trabecular thinning and reduced mechanical strength. These changes were accompanied by increased osteoclast numbers and elevated expression of osteoclast differentiation-related genes (TRAP, NFATc1, Ctsk, FOS). RNA sequencing revealed downregulation of COMMD1 and activation of the NF-κB pathway in TM-infected mice. COMMD1 deficiency exacerbated bone destruction and osteoclast differentiation, while COMMD1 overexpression suppressed these effects. Mechanistic studies showed that COMMD1 deletion increased P65 phosphorylation and decreased IκBα expression, effects that were reversed by JSH-23 treatment.
Conclusion: COMMD1 protects against TM-induced OM by inhibiting the NF-κB pathway, suggesting it as a potential therapeutic target for bone infections.
Keywords: Talaromyces marneffei, COMMD1, osteomyelitis, osteoclast differentiation
1Department of Spine Osteopathia, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China; 2Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry, Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China; 3School of Public Health, Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China; 4Wuming Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Shaohui Zong, Department of Spine Osteopathia, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Qingxiu District, Nanning, Guangxi, 530021, People’s Republic of China, Email zongshaohui@gxmu.edu.cn Gaofeng Zeng, School of Public Health, Guangxi Medical University, No. 22, Shuangyong Road, Qingxiu District, Nanning, Guangxi, 530021, People’s Republic of China, Email zenggaofeng@gxmu.edu.cn
Purpose: This study investigated the role of copper metabolism MURR1 domain-containing 1 (COMMD1) in Talaromyces marneffei (TM)-induced osteomyelitis (OM) and its regulation of osteoclast differentiation via the NF-κB pathway.
Methods: A murine TM infection model was used to assess bone destruction and osteoclast activity via micro-CT, histological analysis, biomechanical testing, qPCR, and Western blot. RNA sequencing was performed to analyze differentially expressed genes. Functional validation was conducted using COMMD1 conditional knockout (cKO) mice and bone marrow-derived monocytes macrophages (BMMs). The NF-κB inhibitor JSH-23 was used to verify pathway dependency.
Results: TM infection significantly upregulated inflammatory cytokines (IL-10, IL-17, TNF-α) and induced severe bone structural damage, characterized by trabecular thinning and reduced mechanical strength. These changes were accompanied by increased osteoclast numbers and elevated expression of osteoclast differentiation-related genes (TRAP, NFATc1, Ctsk, FOS). RNA sequencing revealed downregulation of COMMD1 and activation of the NF-κB pathway in TM-infected mice. COMMD1 deficiency exacerbated bone destruction and osteoclast differentiation, while COMMD1 overexpression suppressed these effects. Mechanistic studies showed that COMMD1 deletion increased P65 phosphorylation and decreased IκBα expression, effects that were reversed by JSH-23 treatment.
Conclusion: COMMD1 protects against TM-induced OM by inhibiting the NF-κB pathway, suggesting it as a potential therapeutic target for bone infections.
Keywords: Talaromyces marneffei, COMMD1, osteomyelitis, osteoclast differentiation