ATF6 aggravates angiogenesis-osteogenesis coupling during ankylosing spondylitis by mediating FGF2 expression in chondrocytes
Mengjun Ma,
Hongyu Li,
Peng Wang,
Wen Yang,
Rujia Mi,
Jiahao Zhuang,
Yuhang Jiang,
Yixuan Lu,
Xin Shen,
Yanfeng Wu,
Huiyong Shen
Affiliations
Mengjun Ma
Department of Orthopedics, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen 518003, China
Hongyu Li
Department of Orthopedics, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen 518003, China
Peng Wang
Department of Orthopedics, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen 518003, China
Wen Yang
Department of Orthopedics, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen 518003, China
Rujia Mi
Center for Biotherapy, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen 518003, China
Jiahao Zhuang
Department of Orthopedics, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen 518003, China
Yuhang Jiang
Department of Orthopedics, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen 518003, China
Yixuan Lu
Center for Biotherapy, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen 518003, China
Xin Shen
Department of Orthopedics, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen 518003, China
Yanfeng Wu
Center for Biotherapy, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen 518003, China; Corresponding author
Huiyong Shen
Department of Orthopedics, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen 518003, China; Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510000, China; Corresponding author
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.
