Abstract
How lineage specifiers are regulated during development is an outstanding question, and the molecular regulation of osteogenic factor RUNX2 remains to be fully understood. Here we report that the Mediator subunit MED23 cooperates with RUNX2 to regulate osteoblast differentiation and bone development. Med23 deletion in mesenchymal stem cells or osteoblast precursors results in multiple bone defects similar to those observed in Runx2+/− mice. In vitro, Med23-deficient progenitor cells are refractory to osteoblast differentiation, and Med23 deficiency reduces Runx2-target gene activity without changing Runx2 expression. Mechanistically, MED23 binds to RUNX2 and modulates its transcriptional activity. Moreover, Med23 deficiency in osteoprogenitor cells exacerbates the skeletal abnormalities observed in Runx2+/− mice. Collectively, our results establish a genetic and physical interaction between RUNX2 and MED23, suggesting that MED23 constitutes a molecular node in the regulatory network of anabolic bone formation and related diseases.
Highlights
How lineage specifiers are regulated during development is an outstanding question, and the molecular regulation of osteogenic factor RUNX2 remains to be fully understood
Our results reveal that MED23 is an important regulator of osteogenesis and is essential for the transcriptional activity of RUNX2
We found that downregulated genes in Med23MSCÀ / À set presented in a similar pattern in Runx[2] þ / À set (Fig. 4b)
Summary
How lineage specifiers are regulated during development is an outstanding question, and the molecular regulation of osteogenic factor RUNX2 remains to be fully understood. The skeletal pathologies in humans and mice highlight the importance of the precise regulation of Runx[2] activity during osteogenesis. Apart from these key transcription factors, several cofactors have been found to be involved in the fine tuning of cell-fate determination[11,12,13]. Our previous research demonstrated that the Mediator MED23 subunit acts as a molecular modulator to control the balance between adipogenesis and myogenesis[15,16] It remained unknown whether MED23 is involved in the development of osteoblasts, which, like adipocytes and myocytes, are derived from mesenchymal progenitors. Our results reveal that MED23 is an important regulator of osteogenesis and is essential for the transcriptional activity of RUNX2
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
