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BRD9-mediated chromatin remodeling suppresses osteoclastogenesis through negative feedback mechanism

Author

Listed:
  • Jiahui Du

    (Shanghai Jiao Tong University School of Medicine
    Shanghai Jiao Tong University
    Shanghai Engineering Research Center of Advanced Dental Technology and Materials)

  • Yili Liu

    (Shanghai Jiao Tong University School of Medicine
    Shanghai Jiao Tong University
    Shanghai Engineering Research Center of Advanced Dental Technology and Materials)

  • Xiaolin Wu

    (Shanghai Jiao Tong University School of Medicine
    Shanghai Jiao Tong University
    Shanghai Engineering Research Center of Advanced Dental Technology and Materials)

  • Jinrui Sun

    (Shanghai Jiao Tong University School of Medicine
    Shanghai Jiao Tong University
    Shanghai Engineering Research Center of Advanced Dental Technology and Materials)

  • Junfeng Shi

    (Shanghai Jiao Tong University School of Medicine
    Shanghai Jiao Tong University
    Shanghai Engineering Research Center of Advanced Dental Technology and Materials)

  • Hongming Zhang

    (Shanghai Jiao Tong University School of Medicine
    Shanghai Jiao Tong University
    Shanghai Engineering Research Center of Advanced Dental Technology and Materials)

  • Ao Zheng

    (Shanghai Jiao Tong University School of Medicine
    Shanghai Jiao Tong University
    Shanghai Engineering Research Center of Advanced Dental Technology and Materials)

  • Mingliang Zhou

    (Shanghai Jiao Tong University School of Medicine
    Shanghai Jiao Tong University
    Shanghai Engineering Research Center of Advanced Dental Technology and Materials)

  • Xinquan Jiang

    (Shanghai Jiao Tong University School of Medicine
    Shanghai Jiao Tong University
    Shanghai Engineering Research Center of Advanced Dental Technology and Materials)

Abstract

Bromodomain-containing protein 9 (BRD9), a component of non-canonical BAF chromatin remodeling complex, has been identified as a critical therapeutic target in hematological diseases. Despite the hematopoietic origin of osteoclasts, the role of BRD9 in osteoclastogenesis and bone diseases remains unresolved. Here, we show Brd9 deficiency in myeloid lineage enhances osteoclast lineage commitment and bone resorption through downregulating interferon-beta (IFN-β) signaling with released constraint on osteoclastogenesis. Notably, we show that BRD9 interacts with transcription factor FOXP1 activating Stat1 transcription and IFN-β signaling thereafter. Besides, function specificity of BRD9 distinguished from BRD4 during osteoclastogenesis has been evaluated. Leveraging advantages of pharmacological modulation of BRD9 and flexible injectable silk fibroin hydrogel, we design a local deliver system for effectively mitigating zoledronate related osteonecrosis of the jaw and alleviating acute bone loss in lipopolysaccharide-induced localized aggressive periodontitis. Overall, these results demonstrate the function of BRD9 in osteoclastogenesis and its therapeutic potential for bone diseases.

Suggested Citation

  • Jiahui Du & Yili Liu & Xiaolin Wu & Jinrui Sun & Junfeng Shi & Hongming Zhang & Ao Zheng & Mingliang Zhou & Xinquan Jiang, 2023. "BRD9-mediated chromatin remodeling suppresses osteoclastogenesis through negative feedback mechanism," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37116-5
    DOI: 10.1038/s41467-023-37116-5
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    References listed on IDEAS

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    1. François Lamoureux & Marc Baud’huin & Lidia Rodriguez Calleja & Camille Jacques & Martine Berreur & Françoise Rédini & Fernando Lecanda & James E. Bradner & Dominique Heymann & Benjamin Ory, 2014. "Selective inhibition of BET bromodomain epigenetic signalling interferes with the bone-associated tumour vicious cycle," Nature Communications, Nature, vol. 5(1), pages 1-14, May.
    2. David E. Place & R. K. Subbarao Malireddi & Jieun Kim & Peter Vogel & Masahiro Yamamoto & Thirumala-Devi Kanneganti, 2021. "Osteoclast fusion and bone loss are restricted by interferon inducible guanylate binding proteins," Nature Communications, Nature, vol. 12(1), pages 1-9, December.
    3. Hiroshi Takayanagi & Sunhwa Kim & Koichi Matsuo & Hiroshi Suzuki & Tomohiko Suzuki & Kojiro Sato & Taeko Yokochi & Hiromi Oda & Kozo Nakamura & Nobutaka Ida & Erwin F. Wagner & Tadatsugu Taniguchi, 2002. "RANKL maintains bone homeostasis through c-Fos-dependent induction of interferon-β," Nature, Nature, vol. 416(6882), pages 744-749, April.
    4. Jovylyn Gatchalian & Shivani Malik & Josephine Ho & Dong-Sung Lee & Timothy W. R. Kelso & Maxim N. Shokhirev & Jesse R. Dixon & Diana C. Hargreaves, 2018. "A non-canonical BRD9-containing BAF chromatin remodeling complex regulates naive pluripotency in mouse embryonic stem cells," Nature Communications, Nature, vol. 9(1), pages 1-16, December.
    5. Simon Makin, 2022. "The destructive power of PROTACs could tackle prostate cancer," Nature, Nature, vol. 609(7927), pages 41-41, September.
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    Cited by:

    1. Jiahui Du & Yili Liu & Jinrui Sun & Enhui Yao & Jingyi Xu & Xiaolin Wu & Ling Xu & Mingliang Zhou & Guangzheng Yang & Xinquan Jiang, 2024. "ARID1A safeguards the canalization of the cell fate decision during osteoclastogenesis," Nature Communications, Nature, vol. 15(1), pages 1-20, December.

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