ATF6 aggravates angiogenesis-osteogenesis coupling during ankylosing spondylitis by mediating FGF2 expression in chondrocytes
2020
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 AS patients. Firstly, we found that ATF6 and fibroblast growth factor 2 (FGF2) levels were higher in SKG mice and AS patient cartilage. The pro-angiogenic ability of human chondrocytes was enhanced through activated ATF6-FGF2 axis following long-term stimulation with inflammatory factors, e.g. TNF-, IFN-{gamma} or 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.
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