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STAT3 is critical for skeletal development and bone homeostasis by regulating osteogenesis

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  • Siru Zhou

    (Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Disease, Shanghai Key Laboratory of Stomatology)

  • Qinggang Dai

    (Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Disease, Shanghai Key Laboratory of Stomatology)

  • Xiangru Huang

    (Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Disease, Shanghai Key Laboratory of Stomatology)

  • Anting Jin

    (Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Disease, Shanghai Key Laboratory of Stomatology)

  • Yiling Yang

    (Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Disease, Shanghai Key Laboratory of Stomatology)

  • Xinyi Gong

    (Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Disease, Shanghai Key Laboratory of Stomatology)

  • Hongyuan Xu

    (Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Disease, Shanghai Key Laboratory of Stomatology)

  • Xin Gao

    (Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Disease, Shanghai Key Laboratory of Stomatology)

  • Lingyong Jiang

    (Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Disease, Shanghai Key Laboratory of Stomatology)

Abstract

Skeletal deformities are typical AD-HIES manifestations, which are mainly caused by heterozygous and loss-of-function mutations in Signal transducer and activator of transcription 3 (STAT3). However, the mechanism is still unclear and the treatment strategy is limited. Herein, we reported that the mice with Stat3 deletion in osteoblasts, but not in osteoclasts, induced AD-HIES-like skeletal defects, including craniofacial malformation, osteoporosis, and spontaneous bone fracture. Mechanistic analyses revealed that STAT3 in cooperation with Msh homeobox 1(MSX1) drove osteoblast differentiation by promoting Distal-less homeobox 5(Dlx5) transcription. Furthermore, pharmacological activation of STAT3 partially rescued skeletal deformities in heterozygous knockout mice, while inhibition of STAT3 aggravated bone loss. Taken together, these data show that STAT3 is critical for modulating skeletal development and maintaining bone homeostasis through STAT3-indcued osteogenesis and suggest it may be a potential target for treatments.

Suggested Citation

  • Siru Zhou & Qinggang Dai & Xiangru Huang & Anting Jin & Yiling Yang & Xinyi Gong & Hongyuan Xu & Xin Gao & Lingyong Jiang, 2021. "STAT3 is critical for skeletal development and bone homeostasis by regulating osteogenesis," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27273-w
    DOI: 10.1038/s41467-021-27273-w
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    References listed on IDEAS

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    1. Zhen Liu & Xiao Yao & Guang Yan & YiChi Xu & Jun Yan & Weiguo Zou & Gang Wang, 2016. "Mediator MED23 cooperates with RUNX2 to drive osteoblast differentiation and bone development," Nature Communications, Nature, vol. 7(1), pages 1-11, September.
    2. Yoshiyuki Minegishi & Masako Saito & Shigeru Tsuchiya & Ikuya Tsuge & Hidetoshi Takada & Toshiro Hara & Nobuaki Kawamura & Tadashi Ariga & Srdjan Pasic & Oliver Stojkovic & Ayse Metin & Hajime Karasuy, 2007. "Dominant-negative mutations in the DNA-binding domain of STAT3 cause hyper-IgE syndrome," Nature, Nature, vol. 448(7157), pages 1058-1062, August.
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