Klf4 haploinsufficiency in Sp7+ lineage leads to underdeveloped mandibles and insufficient elongation of mandibular incisor.

The mandible is an important component of the craniofacial bones, whose development is regulated by complex molecular networks and involves the well-coordinated development of the bone, cartilage, and teeth. Previously, we demonstrated that Krüppel-like factor 4 (KLF4) promoted dentinogenesis and osteogenesis, but it was enigmatic whether Klf4 participated in the development of the mandible. In this study, the Sp7-Cre; Klf4 mice exhibited underdeveloped mandibles and insufficient elongation of the mandibular incisor when compared with Klf4 and Sp7-Cre mice.

BMP2-dependent gene regulatory network analysis reveals Klf4 as a novel transcription factor of osteoblast differentiation.

Transcription factors (TFs) regulate the expression of target genes, inducing changes in cell morphology or activities needed for cell fate determination and differentiation. The BMP signaling pathway is widely regarded as one of the most important pathways in vertebrate skeletal biology, of which BMP2 is a potent inducer, governing the osteoblast differentiation of bone marrow stromal cells (BMSCs). However, the mechanism by which BMP2 initiates its downstream transcription factor cascade and determines the direction of differentiation remains largely unknown.

RUNX2 co-operates with EGR1 to regulate osteogenic differentiation through Htra1 enhancers.

Runt-related transcription factor 2 (Runx2) has been shown to regulate osteoblast differentiation by directly or indirectly regulating numerous osteoblast-related genes. However, our understanding of the transcriptional mechanisms of RUNX2 is mainly restricted to its transactivation, while the mechanism underlying its inhibitory effect during osteoblast differentiation remains largely unknown. Here, we incorporated the anti-RUNX2 chromatin immunoprecipitation (ChIP) sequencing in MC3T3-E1 cells and RNA-sequencing of parietal bone from Runx2 heterozygous mutant mice, to identify the putative genes negatively regulated by RUNX2.

Circulating miR-338 Cluster activities on osteoblast differentiation: Potential Diagnostic and Therapeutic Targets for Postmenopausal Osteoporosis.

MicroRNAs (miRNAs) are the most abundant RNA species found in serum, and recently, several miRNAs have been found to be associated with osteoporosis. However, the development of such associated miRNAs into diagnostic and therapeutic targets remains unaddressed, mostly because of a lack of functional validation. Here, we identified circulating miR-338 associated with postmenopausal osteoporosis, and performed functional validation and .

SP1 regulates KLF4 via SP1 binding motif governed by DNA methylation during odontoblastic differentiation of human dental pulp cells.

Objective: DNA methylation is a critical epigenetic modulation in regulating gene expression in cell differentiation process, however, its detailed molecular mechanism during odontoblastic differentiation remains elusive. We aimed to study the global effect of DNA methylation on odontoblastic differentiation and how DNA methylation affects the transactivation of transcription factor (TF) on its target gene.

Methods: DNA methyltransferase (DNMTs) inhibition assay and following odontoblastic differentiation assay were performed to evaluate the effect of DNA methylation inhibition on odontoblastic differentiation.

miR-3065-5p regulates mouse odontoblastic differentiation partially through bone morphogenetic protein receptor type II.

Illumination of the molecular mechanisms regulating odontoblastic differentiation of dental papilla cells is of great significance for proper dentinogenesis and dental pulp regeneration. In this study, we discovered that microRNA (miR)-3065-5p is up-regulated during odontoblastic differentiation. Overexpression of miR-3065-5p promoted odontoblastic differentiation in vitro.