IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v10y2019i1d10.1038_s41467-018-08277-5.html
   My bibliography  Save this article

Hematopoietic PBX-interacting protein mediates cartilage degeneration during the pathogenesis of osteoarthritis

Author

Listed:
  • Quanbo Ji

    (General Hospital of Chinese People’s Liberation Army
    Beijing Institute of Biotechnology
    Stanford University)

  • Xiaojie Xu

    (Beijing Institute of Biotechnology)

  • Lei Kang

    (Peking University First Hospital)

  • Yameng Xu

    (Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine)

  • Jingbo Xiao

    (National Library of China)

  • Stuart B. Goodman

    (Stanford University)

  • Xiang Zhu

    (Beijing Institute of Biotechnology)

  • Wenchao Li

    (General Hospital of Chinese People’s Liberation Army)

  • Juan Liu

    (Beijing Institute of Biotechnology)

  • Xu Gao

    (Johns Hopkins University School of Medicine)

  • Zhifeng Yan

    (General Hospital of Chinese People’s Liberation Army)

  • Yuxuan Zheng

    (Peking University)

  • Zheng Wang

    (General Hospital of Chinese People’s Liberation Army)

  • William J. Maloney

    (Stanford University)

  • Qinong Ye

    (Beijing Institute of Biotechnology)

  • Yan Wang

    (General Hospital of Chinese People’s Liberation Army)

Abstract

Osteoarthritis (OA) has been recognized as the most common chronic age-related disease. Cartilage degeneration influences OA therapy. Here we report that hematopoietic pre-B cell leukemia transcription factor-interacting protein (HPIP) is essential for OA development. Elevated HPIP levels are found in OA patients. Col2a1-CreERT2/HPIPf/f mice exhibit obvious skeletal abnormalities compared with their HPIPf/f littermates. HPIP deficiency in mice protects against developing OA. Moreover, intra-articular injection of adeno-associated virus carrying HPIP-specific short hairpin RNA in vivo attenuates OA histological signs. Notably, in vitro RNA-sequencing and chromatin immunoprecipitation sequencing profiles identify that HPIP modulates OA cartilage degeneration through transcriptional activation of Wnt target genes. Mechanistically, HPIP promotes the transcription of Wnt targets by interacting with lymphoid enhancer binding factor 1 (LEF1). Furthermore, HPIP potentiates the transcriptional activity of LEF1 and acetylates histone H3 lysine 56 in the promoters of Wnt targets, suggesting that HPIP is an attractive target in OA regulatory network.

Suggested Citation

  • Quanbo Ji & Xiaojie Xu & Lei Kang & Yameng Xu & Jingbo Xiao & Stuart B. Goodman & Xiang Zhu & Wenchao Li & Juan Liu & Xu Gao & Zhifeng Yan & Yuxuan Zheng & Zheng Wang & William J. Maloney & Qinong Ye , 2019. "Hematopoietic PBX-interacting protein mediates cartilage degeneration during the pathogenesis of osteoarthritis," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-018-08277-5
    DOI: 10.1038/s41467-018-08277-5
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-018-08277-5
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-018-08277-5?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
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Donghyun Kang & Jeeyeon Lee & Jisu Jung & Bradley A. Carlson & Moon Jong Chang & Chong Bum Chang & Seung-Baik Kang & Byung Cheon Lee & Vadim N. Gladyshev & Dolph L. Hatfield & Byeong Jae Lee & Jin-Hon, 2022. "Selenophosphate synthetase 1 deficiency exacerbates osteoarthritis by dysregulating redox homeostasis," Nature Communications, Nature, vol. 13(1), 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:10:y:2019:i:1:d:10.1038_s41467-018-08277-5. 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.

    We have no bibliographic references for this item. You can help adding them by using 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.