IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-37116-5.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-37116-5
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-37116-5?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. 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.
    2. 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.
    3. 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.
    4. Simon Makin, 2022. "The destructive power of PROTACs could tackle prostate cancer," Nature, Nature, vol. 609(7927), pages 41-41, September.
    5. 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.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Yawen Lei & Yaoguang Yu & Wei Fu & Tao Zhu & Caihong Wu & Zhihao Zhang & Zewang Yu & Xin Song & Jianqu Xu & Zhenwei Liang & Peitao Lü & Chenlong Li, 2024. "BCL7A and BCL7B potentiate SWI/SNF-complex-mediated chromatin accessibility to regulate gene expression and vegetative phase transition in plants," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    2. Luca Pagliaroli & Patrizia Porazzi & Alyxandra T. Curtis & Chiara Scopa & Harald M. M. Mikkers & Christian Freund & Lucia Daxinger & Sandra Deliard & Sarah A. Welsh & Sarah Offley & Connor A. Ott & Br, 2021. "Inability to switch from ARID1A-BAF to ARID1B-BAF impairs exit from pluripotency and commitment towards neural crest formation in ARID1B-related neurodevelopmental disorders," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    3. Dhurjhoti Saha & Solomon Hailu & Arjan Hada & Junwoo Lee & Jie Luo & Jeff A. Ranish & Yuan-chi Lin & Kyle Feola & Jim Persinger & Abhinav Jain & Bin Liu & Yue Lu & Payel Sen & Blaine Bartholomew, 2023. "The AT-hook is an evolutionarily conserved auto-regulatory domain of SWI/SNF required for cell lineage priming," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    4. Muran Xiao & Shinji Kondo & Masaki Nomura & Shinichiro Kato & Koutarou Nishimura & Weijia Zang & Yifan Zhang & Tomohiro Akashi & Aaron Viny & Tsukasa Shigehiro & Tomokatsu Ikawa & Hiromi Yamazaki & Mi, 2023. "BRD9 determines the cell fate of hematopoietic stem cells by regulating chromatin state," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    5. L. Paige Ferguson & Jovylyn Gatchalian & Matthew L. McDermott & Mari Nakamura & Kendall Chambers & Nirakar Rajbhandari & Nikki K. Lytle & Sara Brin Rosenthal & Michael Hamilton & Sonia Albini & Martin, 2023. "Smarcd3 is an epigenetic modulator of the metabolic landscape in pancreatic ductal adenocarcinoma," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37116-5. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.