机构:[1]Institute for Clinical Chemistry and Laboratory Medicine, Faculty of Medicine, TU Dresden, 01307 Dresden, Germany[2]Department of Basic and Translational Sciences, Laboratory of Innate Immunity and Inflammation, Penn Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA[3]State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Department of Periodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China[4]National Center for Tumor Diseases, Partner Site Dresden, 01307 Dresden, Germany[5]Sheng Yushou Center of Cell Biology and Immunology, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China[6]State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Department of Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China[7]Department of Medicine III & Center for Healthy Aging, Faculty of Medicine, TU Dresden, 01307 Dresden, Germany[8]Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 XZ Nijmegen, the Netherlands[9]Department of Immunology and Metabolism, Life and Medical Sciences Institute, University of Bonn, 53115 Bonn, Germany[10]Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, 01328 Dresden, Germany[11]Paul Langerhans Institute Dresden of the Helmholtz Center Munich, University Hospital and Faculty of Medicine, TU Dresden, 01307 Dresden, Germany[12]German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany
This work was supported by grants from the Stiftung f€ur Pathobiochemie und
Molekulare Diagnostik (to N.H.), the Deutsche Forschungsgemeinschaft (SFBTRR369
to T.C., L.K., M.R., and B.W.) and the NIH (DE031206 and DE033643
to G.H.). T.C. is also supported by the European Research Council
(LOSYSINCHRON), the Saxon State Ministry of Science, Culture and Tourism
(SMWK), and the Deutsche Forschungsgemeinschaft (SFB-TRR332). We
thank Sylvia Grossklaus, Janine Gebler, Despoina Xanthopoulou, Panagiotis
Sidiropoulos, and Charalampos Ioannidis (Institute for Clinical Chemistry
and Laboratory Medicine, Faculty of Medicine, TU Dresden, Dresden, Germany)
for technical assistance and the Dresden Concept Genome Center of not implicate b-glucan-induced TRIM in this context. Our present
study clearly suggests that b-glucan-induced TRIM might also
bear the risk for triggering an ASIA syndrome. Importantly, in
the context of b-glucan therapies, pharmacological MITF inhibition
could prevent trained inflammatory osteoclastogenesis
without in principle interfering with the intended beneficial effects
(e.g., actions against infections or cancer). In conclusion, our
work underscores that detailed understanding of the beneficial
and detrimental actions of b-glucan-induced TRIM and the underlying
molecular mechanisms is imperative for developing
effective therapies that leverage this principle.
Limitations of the study
Our work introduces the concept of innate immune training of (inflammatory)
osteoclastogenesis, which may promote inflammatory
bone loss. Specifically, we found that b-glucan administration
modulated OCP populations in the BM and the spleen. It is
conceivable that the enhanced osteoclastogenesis bias upon
TRIM induction is initiated at the level of earlier BM progenitors,
namely at HSPCs. However, this possibility was not addressed
here and merits future investigations. Additionally, our work
identified that the transcription factor MITF contributes to trained
inflammatory osteoclastogenesis in monocytes. Our conclusion
is based on studies engaging pharmacological MITF inhibition;
this approach bears some limitations, as MITF could be targeted
not only in monocytes but also in additional cells. Future studies
should therefore assess the role of MITF in b-glucan-induced
TRIM and inflammatory osteoclastogenesis by using genetic
tools: for instance, mice with MITF inactivation specifically in
myeloid cells.
RESOURCE AVAILABILITY
Lead contact
Requests for further information and resources should be directed to and will
be fulfilled by the lead contact, Triantafyllos Chavakis (triantafyllos.chavakis@
ukdd.de).
Materials availability
This study did not generate new unique reagents.
Data and code availability
d Data are available upon request to the lead contact.
d Sequencing data are available at the Gene Expression Omnibus
(https://www.ncbi.nlm.nih.gov/geo/) under accession number GEO:
GSE254560.
d Any additional information required to reanalyze the data reported in this
work paper is available from the lead contact upon request.
ACKNOWLEDGMENTS
This work was supported by grants from the Stiftung f€ur Pathobiochemie und
Molekulare Diagnostik (to N.H.), the Deutsche Forschungsgemeinschaft (SFBTRR369
to T.C., L.K., M.R., and B.W.) and the NIH (DE031206 and DE033643
to G.H.). T.C. is also supported by the European Research Council
(LOSYSINCHRON), the Saxon State Ministry of Science, Culture and Tourism
(SMWK), and the Deutsche Forschungsgemeinschaft (SFB-TRR332). We
thank Sylvia Grossklaus, Janine Gebler, Despoina Xanthopoulou, Panagiotis
Sidiropoulos, and Charalampos Ioannidis (Institute for Clinical Chemistry
and Laboratory Medicine, Faculty of Medicine, TU Dresden, Dresden, Germany)
for technical assistance and the Dresden Concept Genome Center of
the TU Dresden. The graphical abstract and figures showing the experimental
design were created using BioRender.com.
语种:
外文
PubmedID:
中科院(CAS)分区:
出版当年[2025]版:
大类|1 区生物学
小类|1 区细胞生物学1 区发育生物学
最新[2025]版:
大类|1 区生物学
小类|1 区细胞生物学1 区发育生物学
第一作者:
第一作者机构:[1]Institute for Clinical Chemistry and Laboratory Medicine, Faculty of Medicine, TU Dresden, 01307 Dresden, Germany
共同第一作者:
通讯作者:
通讯机构:[1]Institute for Clinical Chemistry and Laboratory Medicine, Faculty of Medicine, TU Dresden, 01307 Dresden, Germany[4]National Center for Tumor Diseases, Partner Site Dresden, 01307 Dresden, Germany[10]Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, 01328 Dresden, Germany[11]Paul Langerhans Institute Dresden of the Helmholtz Center Munich, University Hospital and Faculty of Medicine, TU Dresden, 01307 Dresden, Germany[12]German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany
推荐引用方式(GB/T 7714):
Haacke Nora,Wang Hui,Yan Shu,et al.Innate immune training of osteoclastogenesis promotes inflammatory bone loss in mice[J].Developmental Cell.2025,doi:10.1016/j.devcel.2025.02.001.
APA:
Haacke Nora,Wang Hui,Yan Shu,Barovic Marko,Li Xiaofei...&Chavakis Triantafyllos.(2025).Innate immune training of osteoclastogenesis promotes inflammatory bone loss in mice.Developmental Cell,,
MLA:
Haacke Nora,et al."Innate immune training of osteoclastogenesis promotes inflammatory bone loss in mice".Developmental Cell .(2025)