Runx2 plays a central role in Osteoarthritis development

Abstract

Osteoarthritis (OA) is the most common form of arthritis, is the leading cause of impaired mobility in the elderly, and accounts for more than a third of chronic moderate to severe pain. As a degenerative joint disorder, OA affects the whole joint and results in synovial hyperplasia, degradation of articular cartilage, subchondral sclerosis, osteophyte formation, and chronic pain. Currently, there is no effective drug to decelerate OA progression and molecular targets for drug development have been insufficiently investigated. Anti-OA drug development can benefit from more and precise knowledge of molecular targets for drug development. Runt-related transcription factor 2 (Runx2) is a key transcription factor controlling osteoblast and chondrocyte differentiation and is among the most promising potential therapeutic targets. Notably, Runx2 expression is upregulated in several murine OA models, suggesting a role in disease pathogenesis. In this review article, we summarized recent findings on Runx2 related to OA development and evaluated its potential as a therapeutic target. The translational potential of this article A better understanding of the role of Runx2 in osteoarthritis pathogenesis will contribute to the development of novel intervention of osteoarthritis disease.

Species-specific sensitivity to TGFβ signaling and changes to the Mmp13 promoter underlie avian jaw development and evolution

“…(Duan and Derynck, 2019). That being said, our inhibitor experiments further demonstrate that the ability of rTGFβ1 to induce Runx2 and Mmp13 occurs directly via activation of TGFβR1 and phosphorylation of SMAD3, which is something that has been observed previously (Selvamurugan et al, 2004a;Chen et al, 2012b;Di Chen, 2019). Although inhibition of TGFβR1 can lead to upregulation of Runx2 and Mmp13 via a non-canonical p38 MAPK pathway (Chen et al, 2012a), which…”

Overview of MMP-13 as a Promising Target for the Treatment of Osteoarthritis

“…Runt-related transcription factor 2 (Runx2) is a crucial transcription factor associated with OA development [ 61 ]. Hirata et al elucidated its molecular mechanism underlying the endochondral ossification during OA development with the compound knockout of C/EBPb (CCAAT/enhancer-binding protein-b) and Runx2 in mice, showing C/EBPb and RUNX2, with MMP-13 as the target and HIF-2α as the inducer, control cartilage degradation [ 62 ].…”

The Roles of Epigenetics Regulation in Bone Metabolism and Osteoporosis

“…Runt-related transcription factor 2 (RUNX2) and OSX are specific transcription factors necessary for bone formation and osteoblast differentiation, in which OSX is the downstream target of RUNX2 ( Komori, 2019 ; Chen D. et al, 2020 ). During the osteoblast differentiation of MSCs, the level of RUNX2 methylation was decreased, suggesting that RUNX2 methylation plays an important regulatory role in osteoblast differentiation ( Wakitani et al, 2017 ).…”