Regional difference in microRNA regulation in the skull vault

Abstract

Background The murine calvaria has several membrane bones with different tissue origins (e.g., neural crest‐derived frontal bone vs. mesoderm‐derived parietal bone). Neural crest‐derived frontal bone exhibits superior osteogenic activities and bone regeneration. MicroRNA (miRNA) has been emerged as a crucial regulator during organogenesis and is involved in a range of developmental processes. However, the underlying roles of miRNA regulation in frontal bone and parietal bone is unknown. Results Total of 83 significantly expressed known miRNAs were identified in frontal bones versus parietal bones. The significantly enriched gene ontology and KEGG pathway that were predicted by the enrichment miRNAs were involved in several biological processes (cell differentiation, cell adhesion, and transcription), and multiple osteogenic pathways (e.g., focal adhesion, MAPK, VEGF, Wnt, and insulin signaling pathway. Focal adhesion and insulin signaling pathway were selected for target verification and functional analysis, and several genes were predicted to be targets genes by the differentially expressed miRNAs, and these targets genes were tested with significant expressions. Conclusions Our results revealed a novel pattern of miRNAs in murine calvaria with dual tissue origins, and explorations of these miRNAs will be valuable for the translational studies to enhance osteogenic potential and bone regeneration in the clinic.

WITHDRAWN: Efficacy of Chinese Herbal Formulation Combined With Bone Mesenchymal Stem Cells in Repairing Rat Cartilage Tissues

“…In recent years, with the development of regenerative medicine, cell therapy based on bone marrow mesenchymal stem cells has developed rapidly, especially canonical signaling pathways have been demonstrated to be involved in regulation of regenerative medicine [8,10] as well as the microRNA [9].…”

“…However, these treatments can only temporarily relieve pain and improve joint function, but cannot prevent the progress of cartilage defects [4][5][6]. A large number of studies on patients with cartilage defects and animal models of cartilage defects show that a variety of cytokines are involved in the occurrence and development of cartilage defects, such as transforming growth factor-beta (transforming growth factor-beta, TGF-beta) [7][8][9][10]. TGF-beta can signi cantly promote the differentiation of mesenchymal stem cells (MSCs) into cartilage [11,12], and also inhibit the continued differentiation and hypertrophy of mature chondrocytes.…”

Shaping modern human skull through epigenetic, transcriptional and post-transcriptional regulation of the RUNX2 master bone gene

“…On this regard, metopic ossification has been recently shown to be more dependent on Runx2 expression compared to other areas of the skull of knockout murine models 52 . Moreover a recent work demonstrated that selected Runx2-targeting miRNAs may underlie the different osteogenic properties of osteoblasts and precursors isolated from frontal and parietal bones of murine skulls 53 . Therefore, we may speculate that the post-transcriptional modulation of RUNX2 by miR-3150a-3p and miR-6785-5p has evolved in AMH as a site-specific mechanism enabling delayed metopic suture fusion during human skull patterning.…”

BMP Signaling in the Development and Regeneration of Cranium Bones and Maintenance of Calvarial Stem Cells

“…On one hand, the region-dependent roles of evolutionally conserved signaling pathways in calvarial bones are under clarifying (Quarto et al, 2009;Behr et al, 2010;Li et al, 2010;Li et al, 2015). On the other hand, high-throughput sequencing results indicate that generegulatory networks are differently enriched in different segments of calvarial bones (Homayounfar et al, 2015;Hu et al, 2017;Wu et al, 2017;Chen et al, 2019a), both of which have the potential to explain the regional differences upon osteogenic capacities, ossification, and regeneration in the calvarial bones.…”