Regulation and Role of Transcription Factors in Osteogenesis

Abstract

Bone is a dynamic tissue constantly responding to environmental changes such as nutritional and mechanical stress. Bone homeostasis in adult life is maintained through bone remodeling, a controlled and balanced process between bone-resorbing osteoclasts and bone-forming osteoblasts. Osteoblasts secrete matrix, with some being buried within the newly formed bone, and differentiate to osteocytes. During embryogenesis, bones are formed through intramembraneous or endochondral ossification. The former involves a direct differentiation of mesenchymal progenitor to osteoblasts, and the latter is through a cartilage template that is subsequently converted to bone. Advances in lineage tracing, cell sorting, and single-cell transcriptome studies have enabled new discoveries of gene regulation, and new populations of skeletal stem cells in multiple niches, including the cartilage growth plate, chondro-osseous junction, bone, and bone marrow, in embryonic development and postnatal life. Osteoblast differentiation is regulated by a master transcription factor RUNX2 and other factors such as OSX/SP7 and ATF4. Developmental and environmental cues affect the transcriptional activities of osteoblasts from lineage commitment to differentiation at multiple levels, fine-tuned with the involvement of co-factors, microRNAs, epigenetics, systemic factors, circadian rhythm, and the microenvironments. In this review, we will discuss these topics in relation to transcriptional controls in osteogenesis.

Vascularized bone regeneration accelerated by 3D-printed nanosilicate-functionalized polycaprolactone scaffold

“…Moreover, the PCL/LAP scaffold upregulated the expression of RUNX2, ALP and Col-1α1 in BMSCs. RUNX2, a transcription factor involved in bone formation, activates bone-specific gene transcription promoters (including ALP and Col-1α1 ) during the early stage of osteogenic differentiation [ 39 ]. Therefore, it is reasonable to presume that the PCL/LAP scaffold stimulated extracellular matrix mineralization by accelerating Col-1α1 synthesis to provide a matrix for osteoid formation, which might be attributed to the increased RUNX2 level induced by LAP released from PCL/LAP.…”

[Retracted] Exosome: Function and Application in Inflammatory Bone Diseases

“…Exosomes derived from osteoclasts containing miRNA-214 are delivered to osteoblasts through the ephrinA2-EphA2 signaling pathway and negatively regulate ATF4, thereby inhibiting osteogenic activity [ 102 ]. ATF4 is a crucial regulator of bone formation and determines the initiation and terminal differentiation of osteoblasts by transactivating the osteocalcin (OCN) gene and promoting the expression of other osteogenic genes, such as bone sialoprotein (BSP) and OSX [ 103 ]. In addition, lncRNA Hotair is classified as an essential regulator and is highly expressed in serum, which makes it a potential factor for the diagnosis of rheumatoid arthritis by serum assays [ 18 ].…”

Salidroside promotes the osteogenic and odontogenic differentiation of human dental pulp stem cells through the BMP signaling pathway

“…In the present study, the results suggested that RUNX2 was highly expressed during the early stages of hDPSC osteoblast/odontoblastic differentiation following SAL treatment compared with the OM group. RUNX2 and OCN are two extensively studied osteoblast-specific transcription factors that are also key markers of osteoblastic cells ( 38 ). RUNX2 is typically expressed during early osteoblast differentiation and is indispensable for the differentiation and appropriate functioning of osteoblasts ( 38 , 39 ).…”