IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-33744-5.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-33744-5
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-33744-5?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. 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.
    2. 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.
    3. 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.
    4. 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.
    5. 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.
    6. 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.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. B. Edginton-White & A. Maytum & S. G. Kellaway & D. K. Goode & P. Keane & I. Pagnuco & S. A. Assi & L. Ames & M. Clarke & P. N. Cockerill & B. Göttgens & J. B. Cazier & C. Bonifer, 2023. "A genome-wide relay of signalling-responsive enhancers drives hematopoietic specification," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    2. Annkatrin Bressin & Olga Jasnovidova & Mirjam Arnold & Elisabeth Altendorfer & Filip Trajkovski & Thomas A. Kratz & Joanna E. Handzlik & Denes Hnisz & Andreas Mayer, 2023. "High-sensitive nascent transcript sequencing reveals BRD4-specific control of widespread enhancer and target gene transcription," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    3. Victor Lopez Soriano & Alfredo Dueñas Rey & Rajarshi Mukherjee & Frauke Coppieters & Miriam Bauwens & Andy Willaert & Elfride De Baere, 2024. "Multi-omics analysis in human retina uncovers ultraconserved cis-regulatory elements at rare eye disease loci," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    4. Raquel Rouco & Olimpia Bompadre & Antonella Rauseo & Olivier Fazio & Rodrigue Peraldi & Fabrizio Thorel & Guillaume Andrey, 2021. "Cell-specific alterations in Pitx1 regulatory landscape activation caused by the loss of a single enhancer," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    5. Zhe Gong & Jinjin Zhu & Junxin Chen & Fan Feng & Haitao Zhang & Zheyuan Zhang & Chenxin Song & Kaiyu Liang & Shuhui Yang & Shunwu Fan & Xiangqian Fang & Shuying Shen, 2023. "CircRREB1 mediates lipid metabolism related senescent phenotypes in chondrocytes through FASN post-translational modifications," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    6. Yanting Luo & Jianlin He & Xiguang Xu & Ming-an Sun & Xiaowei Wu & Xuemei Lu & Hehuang Xie, 2018. "Integrative single-cell omics analyses reveal epigenetic heterogeneity in mouse embryonic stem cells," PLOS Computational Biology, Public Library of Science, vol. 14(3), pages 1-21, March.
    7. Renata Bordeira-Carriço & Joana Teixeira & Marta Duque & Mafalda Galhardo & Diogo Ribeiro & Rafael D. Acemel & Panos. N. Firbas & Juan J. Tena & Ana Eufrásio & Joana Marques & Fábio J. Ferreira & Telm, 2022. "Multidimensional chromatin profiling of zebrafish pancreas to uncover and investigate disease-relevant enhancers," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    8. Dongmei Wang & Haimin Li & Navdeep S. Chandel & Yali Dou & Rui Yi, 2023. "MOF-mediated histone H4 Lysine 16 acetylation governs mitochondrial and ciliary functions by controlling gene promoters," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    9. Kota Hamamoto & Yusuke Umemura & Shiho Makino & Takashi Fukaya, 2023. "Dynamic interplay between non-coding enhancer transcription and gene activity in development," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    10. Ming-liang Ji & Hua Jiang & Zhuang Li & Rui Geng & Jun Zheng Hu & Yu Cheng Lin & Jun Lu, 2022. "Sirt6 attenuates chondrocyte senescence and osteoarthritis progression," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    11. Michael S. Werner & Tobias Loschko & Thomas King & Shelley Reich & Tobias Theska & Mirita Franz-Wachtel & Boris Macek & Ralf J. Sommer, 2023. "Histone 4 lysine 5/12 acetylation enables developmental plasticity of Pristionchus mouth form," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    12. Mattia Zaghi & Federica Banfi & Luca Massimino & Monica Volpin & Edoardo Bellini & Simone Brusco & Ivan Merelli & Cristiana Barone & Michela Bruni & Linda Bossini & Luigi Antonio Lamparelli & Laura Pi, 2023. "Balanced SET levels favor the correct enhancer repertoire during cell fate acquisition," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    13. Charles Limouse & Owen K. Smith & David Jukam & Kelsey A. Fryer & William J. Greenleaf & Aaron F. Straight, 2023. "Global mapping of RNA-chromatin contacts reveals a proximity-dominated connectivity model for ncRNA-gene interactions," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    14. Chaitali Chakraborty & Itzel Nissen & Craig A. Vincent & Anna-Carin Hägglund & Andreas Hörnblad & Silvia Remeseiro, 2023. "Rewiring of the promoter-enhancer interactome and regulatory landscape in glioblastoma orchestrates gene expression underlying neurogliomal synaptic communication," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    15. Zia-Ur-Rehman & Muhammad Razzaq Athar & M. Mohsin Shahid & Malik Muhammad Faisal & Mareum Shehzadi, 2022. "Exploring The Serial Mediation Of Mobile App Engagement And Self Brand Connection In The Relationship Between Brand Experience And Loyalty Towards Brand," Bulletin of Business and Economics (BBE), Research Foundation for Humanity (RFH), vol. 11(2), pages 20-30, June.
    16. Vladyslava Gorbovytska & Seung-Kyoon Kim & Filiz Kuybu & Michael Götze & Dahun Um & Keunsoo Kang & Andreas Pittroff & Theresia Brennecke & Lisa-Marie Schneider & Alexander Leitner & Tae-Kyung Kim & Cl, 2022. "Enhancer RNAs stimulate Pol II pause release by harnessing multivalent interactions to NELF," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
    17. Milan Kumar Samanta & Srimonta Gayen & Clair Harris & Emily Maclary & Yumie Murata-Nakamura & Rebecca M. Malcore & Robert S. Porter & Patricia M. Garay & Christina N. Vallianatos & Paul B. Samollow & , 2022. "Activation of Xist by an evolutionarily conserved function of KDM5C demethylase," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    18. Masaki Kikuchi & Satoshi Morita & Masatoshi Wakamori & Shin Sato & Tomomi Uchikubo-Kamo & Takehiro Suzuki & Naoshi Dohmae & Mikako Shirouzu & Takashi Umehara, 2023. "Epigenetic mechanisms to propagate histone acetylation by p300/CBP," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    19. Marko Dunjić & Felix Jonas & Gilad Yaakov & Roye More & Yoav Mayshar & Yoach Rais & Ayelet-Hashahar Orenbuch & Saifeng Cheng & Naama Barkai & Yonatan Stelzer, 2023. "Histone exchange sensors reveal variant specific dynamics in mouse embryonic stem cells," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    20. Lasse K. Markussen & Elizabeth A. Rondini & Olivia Sveidahl Johansen & Jesper G. S. Madsen & Elahu G. Sustarsic & Ann-Britt Marcher & Jacob B. Hansen & Zachary Gerhart-Hines & James G. Granneman & Sus, 2022. "Lipolysis regulates major transcriptional programs in brown adipocytes," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33744-5. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.