IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-48255-8.html
   My bibliography  Save this article

Targeting adipocyte ESRRA promotes osteogenesis and vascular formation in adipocyte-rich bone marrow

Author

Listed:
  • Tongling Huang

    (Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences)

  • Zhaocheng Lu

    (Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences)

  • Zihui Wang

    (Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Lixin Cheng

    (Shenzhen Clinical Research Center for Geriatrics, Shenzhen People’s Hospital)

  • Lu Gao

    (Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Jun Gao

    (Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences)

  • Ning Zhang

    (Shantou University Medical College)

  • Chang-An Geng

    (Kunming Institute of Botany, Chinese Academy of Sciences)

  • Xiaoli Zhao

    (Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences)

  • Huaiyu Wang

    (Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences)

  • Chi-Wai Wong

    (Guangzhou Huazhen Biosciences)

  • Kelvin W. K. Yeung

    (Li Ka Shing Faculty of Medicine, The University of Hong Kong)

  • Haobo Pan

    (Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences)

  • William Weijia Lu

    (Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences)

  • Min Guan

    (Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

Abstract

Excessive bone marrow adipocytes (BMAds) accumulation often occurs under diverse pathophysiological conditions associated with bone deterioration. Estrogen-related receptor α (ESRRA) is a key regulator responding to metabolic stress. Here, we show that adipocyte-specific ESRRA deficiency preserves osteogenesis and vascular formation in adipocyte-rich bone marrow upon estrogen deficiency or obesity. Mechanistically, adipocyte ESRRA interferes with E2/ESR1 signaling resulting in transcriptional repression of secreted phosphoprotein 1 (Spp1); yet positively modulates leptin expression by binding to its promoter. ESRRA abrogation results in enhanced SPP1 and decreased leptin secretion from both visceral adipocytes and BMAds, concertedly dictating bone marrow stromal stem cell fate commitment and restoring type H vessel formation, constituting a feed-forward loop for bone formation. Pharmacological inhibition of ESRRA protects obese mice against bone loss and high marrow adiposity. Thus, our findings highlight a therapeutic approach via targeting adipocyte ESRRA to preserve bone formation especially in detrimental adipocyte-rich bone milieu.

Suggested Citation

  • Tongling Huang & Zhaocheng Lu & Zihui Wang & Lixin Cheng & Lu Gao & Jun Gao & Ning Zhang & Chang-An Geng & Xiaoli Zhao & Huaiyu Wang & Chi-Wai Wong & Kelvin W. K. Yeung & Haobo Pan & William Weijia Lu, 2024. "Targeting adipocyte ESRRA promotes osteogenesis and vascular formation in adipocyte-rich bone marrow," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48255-8
    DOI: 10.1038/s41467-024-48255-8
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-48255-8
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-48255-8?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. Matthew J. Emmett & Hee-Woong Lim & Jennifer Jager & Hannah J. Richter & Marine Adlanmerini & Lindsey C. Peed & Erika R. Briggs & David J. Steger & Tao Ma & Carrie A. Sims & Joseph A. Baur & Liming Pe, 2017. "Histone deacetylase 3 prepares brown adipose tissue for acute thermogenic challenge," Nature, Nature, vol. 546(7659), pages 544-548, June.
    2. Bingyang Dai & Jiankun Xu & Xu Li & Le Huang & Chelsea Hopkins & Honglian Wang & Hao Yao & Jie Mi & Lizhen Zheng & Jiali Wang & Wenxue Tong & Dick Ho-kiu Chow & Ye Li & Xuan He & Peijie Hu & Ziyi Chen, 2022. "Macrophages in epididymal adipose tissue secrete osteopontin to regulate bone homeostasis," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    3. Hui Xia & Charlotte Scholtes & Catherine R. Dufour & Carlo Ouellet & Majid Ghahremani & Vincent Giguère, 2022. "Insulin action and resistance are dependent on a GSK3β-FBXW7-ERRα transcriptional axis," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    4. Olaia Naveiras & Valentina Nardi & Pamela L. Wenzel & Peter V. Hauschka & Frederic Fahey & George Q. Daley, 2009. "Bone-marrow adipocytes as negative regulators of the haematopoietic microenvironment," Nature, Nature, vol. 460(7252), pages 259-263, July.
    5. Karla J. Suchacki & Adriana A. S. Tavares & Domenico Mattiucci & Erica L. Scheller & Giorgos Papanastasiou & Calum Gray & Matthew C. Sinton & Lynne E. Ramage & Wendy A. McDougald & Andrea Lovdel & Ric, 2020. "Bone marrow adipose tissue is a unique adipose subtype with distinct roles in glucose homeostasis," Nature Communications, Nature, vol. 11(1), pages 1-18, December.
    6. Shaopeng Yuan & Katherine S. Stewart & Yihao Yang & Merve Deniz Abdusselamoglu & S. Martina Parigi & Tamar Y. Feinberg & Karen Tumaneng & Hanseul Yang & John M. Levorse & Lisa Polak & David Ng & Elain, 2022. "Ras drives malignancy through stem cell crosstalk with the microenvironment," Nature, Nature, vol. 612(7940), pages 555-563, December.
    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. Tammy Liu & Gerd Melkus & Tim Ramsay & Adnan Sheikh & Odette Laneuville & Guy Trudel, 2023. "Bone marrow adiposity modulation after long duration spaceflight in astronauts," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. Yong Geun Jeon & Hahn Nahmgoong & Jiyoung Oh & Dabin Lee & Dong Wook Kim & Jane Eunsoo Kim & Ye Young Kim & Yul Ji & Ji Seul Han & Sung Min Kim & Jee Hyung Sohn & Won Taek Lee & Sun Won Kim & Jeu Park, 2024. "Ubiquitin ligase RNF20 coordinates sequential adipose thermogenesis with brown and beige fat-specific substrates," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    3. Hui Xia & Catherine R. Dufour & Younes Medkour & Charlotte Scholtes & Yonghong Chen & Christina Guluzian & Wafa B’chir & Vincent Giguère, 2023. "Hepatocyte FBXW7-dependent activity of nutrient-sensing nuclear receptors controls systemic energy homeostasis and NASH progression in male mice," Nature Communications, Nature, vol. 14(1), pages 1-24, December.
    4. Yonggang Fan & Weixin Zhang & Xiusheng Huang & Mingzhe Fan & Chenhao Shi & Lantian Zhao & Guofu Pi & Huafeng Zhang & Shuangfei Ni, 2024. "Senescent-like macrophages mediate angiogenesis for endplate sclerosis via IL-10 secretion in male mice," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    5. N. Zioni & A. Akhiad Bercovich & N. Chapal-Ilani & Tal Bacharach & N. Rappoport & A. Solomon & R. Avraham & E. Kopitman & Z. Porat & M. Sacma & G. Hartmut & M. Scheller & C. Muller-Tidow & D. Lipka & , 2023. "Inflammatory signals from fatty bone marrow support DNMT3A driven clonal hematopoiesis," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    6. Trent D. Hall & Hyunjin Kim & Mahmoud Dabbah & Jacquelyn A. Myers & Jeremy Chase Crawford & Antonio Morales-Hernandez & Claire E. Caprio & Pramika Sriram & Emilia Kooienga & Marta Derecka & Esther A. , 2022. "Murine fetal bone marrow does not support functional hematopoietic stem and progenitor cells until birth," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    7. Kei Kohno & Hiroto Narimatsu & Yosuke Shiono & Ikuko Suzuki & Yuichi Kato & Ri Sho & Katsumi Otani & Kenichi Ishizawa & Hidetoshi Yamashita & Isao Kubota & Yoshiyuki Ueno & Takeo Kato & Akira Fukao & , 2016. "High Serum Adiponectin Level Is a Risk Factor for Anemia in Japanese Men: A Prospective Observational Study of 1,029 Japanese Subjects," PLOS ONE, Public Library of Science, vol. 11(12), pages 1-14, 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:15:y:2024:i:1:d:10.1038_s41467-024-48255-8. 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.