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bioRxiv · 10.1101/2020.10.08.332379

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

Ma, M.·Li, H.·Wang, P.·Yang, W.·Mi, R.·Jiang, Y.·Lu, Y.·Shen, X.·Sui, P.·Wu, Y.·Shen, H.
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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 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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Ma, M., Li, H., Wang, P., Yang, W., Mi, R., Jiang, Y., Lu, Y., Shen, X., Sui, P., Wu, Y., Shen, H.. 2020-10-08. ATF6 aggravates angiogenesis-osteogenesis coupling during ankylosing spondylitis by mediating FGF2 expression in chondrocytes. https://doi.org/10.1101/2020.10.08.332379

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