TY - JOUR
T1 - Runx2 and Runx3 differentially regulate articular chondrocytes during surgically induced osteoarthritis development
AU - Nagata, Kosei
AU - Hojo, Hironori
AU - Chang, Song Ho
AU - Okada, Hiroyuki
AU - Yano, Fumiko
AU - Chijimatsu, Ryota
AU - Omata, Yasunori
AU - Mori, Daisuke
AU - Makii, Yuma
AU - Kawata, Manabu
AU - Kaneko, Taizo
AU - Iwanaga, Yasuhide
AU - Nakamoto, Hideki
AU - Maenohara, Yuji
AU - Tachibana, Naohiro
AU - Ishikura, Hisatoshi
AU - Higuchi, Junya
AU - Taniguchi, Yuki
AU - Ohba, Shinsuke
AU - Chung, Ung il
AU - Tanaka, Sakae
AU - Saito, Taku
N1 - Funding Information:
We thank J. Sugita, R. Homma, A. Ogikubo, and K. Kaneko for technical assistance. We thank Ashleigh Cooper, PhD, from Edanz ( https://jp.edanz.com/ac ) for editing a draft of this manuscript. This work was supported by JSPS KAKENHI Grant Numbers 19H05654, 19H05565, 18KK0254, 17H04310, 20H03799, 20K09428, and 20K09451.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-022-33744-5
DO - 10.1038/s41467-022-33744-5
M3 - Article
C2 - 36261443
AN - SCOPUS:85140217824
SN - 2041-1723
VL - 13
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 6187
ER -