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 ChungSakae Tanaka, Taku Saito

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number6187
JournalNature communications
Volume13
Issue number1
DOIs
Publication statusPublished - Dec 2022

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • General
  • Physics and Astronomy(all)

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