Runx3 regulates chondrocyte phenotype by controlling multiple genes involved in chondrocyte proliferation and differentiation.

Abstract

Chondrocytes are the sole cell type present within cartilage, and play pivotal roles in controlling the formation and composition of health cartilage. Chondrocytes maintain cartilage homeostasis through proliferating, differentiating and synthesizing different types of extracellular matrices. Thus, the coordinated proliferation and differentiation of chondrocytes are essential for cartilage growth, repair and the conversion from cartilage to bone during the processes of bone formation and fracture healing. Runx3, a transcription factor that belongs to the Runx family, is significantly upregulated at the onset of cartilage mineralization and regulates both early and late markers of chondrocyte maturation. Therefore, Runx3 may serve as an accelerator of chondrocyte differentiation and maturation. However, the underlying molecular mechanism of Runx3 in regulating chondrocyte proliferation and differentiation remains largely to be elucidated. In the present study, we used state-of-the-art RNA-seq technology combined with validation methods to investigate the effect of Runx3 overexpression or silencing on primary chondrocyte proliferation and differentiation, and demonstrated that Runx3 overexpression possibly inhibited chondrocyte proliferation but accelerated differentiation, whereas Runx3 silencing possibly promoted chondrocyte proliferation but suppressed differentiation. Furthermore, Runx3 overexpression possibly decreased the expression levels of Sox9 and its downstream genes via Sox9 cartilage-specific enhancers, and vice versa for Runx3 silencing.