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Runx2 and Runx3 differentially regulate articular chondrocytes during surgically induced osteoarthritis development

Author

Listed:
  • Kosei Nagata

    (The University of Tokyo)

  • Hironori Hojo

    (The University of Tokyo)

  • Song Ho Chang

    (The University of Tokyo)

  • Hiroyuki Okada

    (The University of Tokyo
    The University of Tokyo)

  • Fumiko Yano

    (The University of Tokyo)

  • Ryota Chijimatsu

    (The University of Tokyo)

  • Yasunori Omata

    (The University of Tokyo
    The University of Tokyo)

  • Daisuke Mori

    (The University of Tokyo)

  • Yuma Makii

    (The University of Tokyo)

  • Manabu Kawata

    (The University of Tokyo)

  • Taizo Kaneko

    (The University of Tokyo)

  • Yasuhide Iwanaga

    (The University of Tokyo)

  • Hideki Nakamoto

    (The University of Tokyo)

  • Yuji Maenohara

    (The University of Tokyo)

  • Naohiro Tachibana

    (The University of Tokyo)

  • Hisatoshi Ishikura

    (The University of Tokyo)

  • Junya Higuchi

    (The University of Tokyo)

  • Yuki Taniguchi

    (The University of Tokyo)

  • Shinsuke Ohba

    (The University of Tokyo
    Nagasaki University)

  • Ung-il Chung

    (Nagasaki University)

  • Sakae Tanaka

    (The University of Tokyo)

  • Taku Saito

    (The University of Tokyo)

Abstract

The Runt-related transcription factor (Runx) family plays various roles in the homeostasis of cartilage. Here, we examined the role of Runx2 and Runx3 for osteoarthritis development in vivo and in vitro. Runx3-knockout mice exhibited accelerated osteoarthritis following surgical induction, accompanied by decreased expression of lubricin and aggrecan. Meanwhile, Runx2 conditional knockout mice showed biphasic phenotypes: heterozygous knockout inhibited osteoarthritis and decreased matrix metallopeptidase 13 (Mmp13) expression, while homozygous knockout of Runx2 accelerated osteoarthritis and reduced type II collagen (Col2a1) expression. Comprehensive transcriptional analyses revealed lubricin and aggrecan as transcriptional target genes of Runx3, and indicated that Runx2 sustained Col2a1 expression through an intron 6 enhancer when Sox9 was decreased. Intra-articular administration of Runx3 adenovirus ameliorated development of surgically induced osteoarthritis. Runx3 protects adult articular cartilage through extracellular matrix protein production under normal conditions, while Runx2 exerts both catabolic and anabolic effects under the inflammatory condition.

Suggested Citation

  • Kosei Nagata & Hironori Hojo & Song Ho Chang & Hiroyuki Okada & Fumiko Yano & Ryota Chijimatsu & Yasunori Omata & Daisuke Mori & Yuma Makii & Manabu Kawata & Taizo Kaneko & Yasuhide Iwanaga & Hideki N, 2022. "Runx2 and Runx3 differentially regulate articular chondrocytes during surgically induced osteoarthritis development," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33744-5
    DOI: 10.1038/s41467-022-33744-5
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    References listed on IDEAS

    as
    1. Alvaro Rada-Iglesias & Ruchi Bajpai & Tomek Swigut & Samantha A. Brugmann & Ryan A. Flynn & Joanna Wysocka, 2011. "A unique chromatin signature uncovers early developmental enhancers in humans," Nature, Nature, vol. 470(7333), pages 279-283, February.
    2. Hiroshi Kobayashi & Song Ho Chang & Daisuke Mori & Shozo Itoh & Makoto Hirata & Yoko Hosaka & Yuki Taniguchi & Keita Okada & Yoshifumi Mori & Fumiko Yano & Ung-il Chung & Haruhiko Akiyama & Hiroshi Ka, 2016. "Biphasic regulation of chondrocytes by Rela through induction of anti-apoptotic and catabolic target genes," Nature Communications, Nature, vol. 7(1), pages 1-12, December.
    3. Manoj Arra & Gaurav Swarnkar & Ke Ke & Jesse E. Otero & Jun Ying & Xin Duan & Takashi Maruyama & Muhammad Farooq Rai & Regis J. O’Keefe & Gabriel Mbalaviele & Jie Shen & Yousef Abu-Amer, 2020. "LDHA-mediated ROS generation in chondrocytes is a potential therapeutic target for osteoarthritis," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    4. Jian Huang & Lan Zhao & Yunshan Fan & Lifan Liao & Peter X. Ma & Guozhi Xiao & Di Chen, 2019. "The microRNAs miR-204 and miR-211 maintain joint homeostasis and protect against osteoarthritis progression," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    5. Tae-Kyung Kim & Martin Hemberg & Jesse M. Gray & Allen M. Costa & Daniel M. Bear & Jing Wu & David A. Harmin & Mike Laptewicz & Kellie Barbara-Haley & Scott Kuersten & Eirene Markenscoff-Papadimitriou, 2010. "Widespread transcription at neuronal activity-regulated enhancers," Nature, Nature, vol. 465(7295), pages 182-187, May.
    6. Sho Mokuda & Ryo Nakamichi & Tokio Matsuzaki & Yoshiaki Ito & Tempei Sato & Kohei Miyata & Masafumi Inui & Merissa Olmer & Eiji Sugiyama & Martin Lotz & Hiroshi Asahara, 2019. "Wwp2 maintains cartilage homeostasis through regulation of Adamts5," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
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