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

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 Nakamoto, Yuji Maenohara, Naohiro Tachibana, Hisatoshi Ishikura, Junya Higuchi, Yuki Taniguchi, Shinsuke Ohba, Ung-il Chung, Sakae Tanaka and Taku Saito ()
Additional contact information
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
Fumiko Yano: The University of Tokyo
Ryota Chijimatsu: The University of Tokyo
Yasunori Omata: 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
Ung-il Chung: Nagasaki University
Sakae Tanaka: The University of Tokyo
Taku Saito: The University of Tokyo

Nature Communications, 2022, vol. 13, issue 1, 1-17

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-33744-5

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