ATF6 aggravates angiogenesis-osteogenesis coupling during ankylosing spondylitis by mediating FGF2 expression in chondrocytes

• Main Authors: Mengjun Ma, Hongyu Li, Peng Wang, Wen Yang, Rujia Mi, Jiahao Zhuang, Yuhang Jiang, Yixuan Lu, Xin Shen, Yanfeng Wu, Huiyong Shen
• Format: Article
• Language: English
• Published: Elsevier 2021-07-01
• Series: iScience
• Subjects: Biological sciences; Physiology; Molecular biology
• Online Access: http://www.sciencedirect.com/science/article/pii/S2589004221007598

Summary: Although angiogenesis-osteogenesis coupling is important in ankylosing spondylitis (AS), therapeutic agents targeting the vasculature remain elusive. Here, we identified activating transcription factor 6 (ATF6) as an important regulator of angiogenesis in the pathogenesis of AS. First, we found that ATF6 and fibroblast growth factor 2 (FGF2) levels were higher in SKG mice and in cartilage of pateints with AS1. The proangiogenic activity of human chondrocytes was enhanced by the activation of the ATF6-FGF2 axis following 7 days of stimulation with inflammatory factors, e.g., tumor necrosis factor alpha (TNF-α), interferon-γ (IFN-γ) or interleukin-17 (IL-17). Mechanistically, ATF6 interacted with the FGF2 promotor and promoted its transcription. Treatment with the ATF6 inhibitor Ceapin-A7 inhibited angiogenesis in vitro and angiogenesis-osteogenesis coupling in vivo. ATF6 may aggravate angiogenesis-osteogenesis coupling during AS by mediating FGF2 transcription in chondrocytes, implying that ATF6 represents a promising therapeutic target for AS.