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

doi:10.1016/j.isci.2021.102791

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

iScience. 2021 Jun 28;24(7):102791. doi: 10.1016/j.isci.2021.102791. eCollection 2021 Jul 23.

Authors

Mengjun Ma¹, Hongyu Li¹, Peng Wang¹, Wen Yang¹, Rujia Mi², Jiahao Zhuang¹, Yuhang Jiang¹, Yixuan Lu², Xin Shen¹, Yanfeng Wu², Huiyong Shen^{1

3}

Affiliations

¹ Department of Orthopedics, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen 518003, China.
² Center for Biotherapy, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen 518003, China.
³ Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510000, China.

Abstract

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.

Keywords: Biological sciences; Molecular biology; Physiology.