RRC ID 59714
Author Yano F, Ohba S, Murahashi Y, Tanaka S, Saito T, Chung UI.
Title Runx1 contributes to articular cartilage maintenance by enhancement of cartilage matrix production and suppression of hypertrophic differentiation.
Journal Sci Rep
Abstract Osteoarthritis (OA) results from an imbalance of the dynamic equilibrium between the breakdown and repair of joint tissues. Previously, we reported that Runx1 enhanced chondrogenic differentiation through transcriptional induction of COL2A1, and suppressed hypertrophic differentiation. Here, we investigated the involvement of Runx1 in OA development as well as its potential underlying molecular mechanism. When we analysed OA development in Col2a1-Cre;Runx1fl/fl and Runx1fl/fl mice by surgically inducing joint instability, Cartilage degradation and osteophyte formation of Col2a1-Cre;Runx1fl/fl joints was accelerated compared with joints in Runx1fl/fl animals 8 weeks after surgery. To investigate chondrocyte regulation by Runx1, we analysed interactions with co-factors and downstream molecules. Runx1 enhanced cartilage matrix production in cooperation with Sox5, Sox6, and Sox9, and co-immunoprecipitation assays showed protein-protein binding between Runx1 and each Sox protein. Knockdown of Runx1 increased expression of a hypertrophic marker, Co10a1, in mouse articular cartilage and primary chondrocytes. This expression was accompanied by decreased expression of Bapx1, a potent suppressor of hypertrophic differentiation. Notably, Runx1-induced suppression of hypertrophic differentiation was diminished by siRNA silencing of Bapx1, whereas chondrogenic markers were unaltered. Thus, Runx1 contributes to articular cartilage maintenance by enhancing matrix production in cooperation with Sox proteins, and suppressing hypertrophic differentiation at least partly via Bapx1 induction.
Volume 9(1)
Pages 7666
Published 2019-5-21
DOI 10.1038/s41598-019-43948-3
PII 10.1038/s41598-019-43948-3
PMID 31113964
PMC PMC6529519
MeSH Animals Cartilage, Articular / cytology Cartilage, Articular / metabolism* Cell Differentiation* Cells, Cultured Chondrocytes / cytology Chondrocytes / metabolism Chondrogenesis Collagen Type II / genetics Collagen Type II / metabolism Core Binding Factor Alpha 2 Subunit / genetics Core Binding Factor Alpha 2 Subunit / metabolism* Homeodomain Proteins / genetics Homeodomain Proteins / metabolism Humans Mice Mice, Inbred C57BL Osteoarthritis / genetics Osteoarthritis / metabolism* Osteoarthritis / pathology SOX Transcription Factors / genetics SOX Transcription Factors / metabolism Transcription Factors / genetics Transcription Factors / metabolism
IF 4.011
Times Cited 2
Human and Animal Cells 10T1/2(RCB0247) ATDC5(RCB0565)