MICROmanagement of Runx2 Function in Skeletal Cells

Abstract

Purpose of Review-Precise and temporal expression of Runx2 and its regulatory transcriptional network is a key determinant for the intricate cellular and developmental processes in adult bone tissue formation. This review analyzes how microRNA functions to regulate this network, and how dysregulation results in bone disorders. Recent Findings-Similar to other biologic processes, microRNA (miRNA/miR) regulation is undeniably indispensable to bone synthesis and maintenance. There exists a miRNA-RUNX2 network where RUNX2 regulates the transcription of miRs, or is post transcriptionally regulated by a class of miRs, forming a variety of miR-RUNX2 regulatory pathways which regulate osteogenesis. Summary-The current review provides insights to understand transcriptional-post transcriptional regulatory network governed by Runx2 and osteogenic miRs, and is based largely from in vitro and in vivo studies. When taken together, this article discusses a new regulatory layer of bone tissue specific gene expression by RUNX2 influenced via miRNA.

Nobiletin promotes osteogenic differentiation of human osteoblastic cell line (MG-63) through activating the BMP-2/RUNX-2 signaling pathway

“…The dynamic balances between these two kinds of cell outcomes are implicated in bone remodeling ( Macias et al, 2020 ). Osteoporosis is a decrease in bone accumulation due to a disparity amongst bone formation and bone resorption, while bone homeostasis need sense of balance connections among osteoclasts and osteoblasts (​ Wildman et al, 2019 ). Existing drugs are employed to cure osteoporosis consist of calcitonin, estrogen, bisphosphonates and ipriflavone.…”

3D printed biocompatible graphene oxide, attapulgite, and collagen composite scaffolds for bone regeneration

“…58,59 Runx-2 is a positive regulator that upregulates bone matrix protein expression. 60 Osteocalcin (OCN) plays an important regulatory role in the formation of ECM proteins and the mineralization of bone tissue during bone formation. 61 Osterix is a transcription factor specifically expressed downstream of Runx2 in bone tissue and plays an important role in the differentiation of preosteoblasts into osteoblasts.…”

Baf45a Mediated Chromatin Remodeling Promotes Transcriptional Activation for Osteogenesis and Odontogenesis

“…( 51 ). For inducible deletion of Baf45a , the tamoxifen-inducible ubiquitously expressing CAGGCre-ER™ (JAX stock #004682) ( 36 ) mouse was bread into the Baf45a f/f mouse line. Primary calvarial cells were subsequently isolated and either treated with 1µM 4-OH tamoxifen (72 hours, refreshed media daily) or with an equal volume of ethanol as a mock treatment and differentiated in osteogenic media for 3 and 10 days.…”

“…Baf45a wild type and knockout calvarial cells were assayed for chromatin accessibility using the Assay for Transposase Accessible Chromatin sequencing (ATAC-seq) technique as described by Buenrostro et al (51). For inducible deletion of Baf45a, the tamoxifen-inducible ubiquitously expressing CAGGCre-ER ™ (JAX stock #004682) (36) mouse was bread into the Baf45a f/f mouse line. Primary calvarial cells were subsequently isolated and either treated with 1µM 4-OH tamoxifen (72 hours, refreshed media daily) or with an equal volume of ethanol as a mock treatment and differentiated in osteogenic media for 3 and 10 days.…”

“…Much of what we know about the regulation of this gene program comes from our understanding of the bone gene transcriptional program and bonetissue-specific signaling (30,31). Furthermore, growing studies about the epigenetic regulation involved in osteogenesis primarily focus on histone post-translational modifications, miRNA, and non-coding RNAs (32)(33)(34)(35)(36)(37)(38)(39). However, the tissue-specific mechanisms involved in the openness of the chromatin around active genes are understudied in osteogenesis.…”