2. Academic Validation
  3. STAT3 is critical for skeletal development and bone homeostasis by regulating osteogenesis

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

  • Nat Commun. 2021 Nov 25;12(1):6891. doi: 10.1038/s41467-021-27273-w.
Siru Zhou  # 1,  Qinggang Dai  # 2,  Xiangru Huang  # 1,  Anting Jin  # 1,  Yiling Yang 1,  Xinyi Gong 1,  Hongyuan Xu 1,  Xin Gao 1,  Lingyong Jiang 3
Affiliations

Affiliations

  • 1 Center of Craniofacial Orthodontics, Department of Oral and Cranio-maxillofacial Science, 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, Shanghai, 200011, China.
  • 2 2nd Dental Center, 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, Shanghai, 200011, China.
  • 3 Center of Craniofacial Orthodontics, Department of Oral and Cranio-maxillofacial Science, 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, Shanghai, 200011, China. jianglingyong@sjtu.edu.cn.
  • # Contributed equally.
PMID: 34824272 DOI: 10.1038/s41467-021-27273-w
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.

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