Cell signaling and transcriptional regulation of osteoblast lineage commitment, differentiation, bone formation, and homeostasis

Abstract

The initiation of osteogenesis primarily occurs as mesenchymal stem cells undergo differentiation into osteoblasts. This differentiation process plays a crucial role in bone formation and homeostasis and is regulated by two intricate processes: cell signal transduction and transcriptional gene expression. Various essential cell signaling pathways, including Wnt, BMP, TGF-β, Hedgehog, PTH, FGF, Ephrin, Notch, Hippo, and Piezo1/2, play a critical role in facilitating osteoblast differentiation, bone formation, and bone homeostasis. Key transcriptional factors in this differentiation process include Runx2, Cbfβ, Runx1, Osterix, ATF4, SATB2, and TAZ/YAP. Furthermore, a diverse array of epigenetic factors also plays critical roles in osteoblast differentiation, bone formation, and homeostasis at the transcriptional level. This review provides an overview of the latest developments and current comprehension concerning the pathways of cell signaling, regulation of hormones, and transcriptional regulation of genes involved in the commitment and differentiation of osteoblast lineage, as well as in bone formation and maintenance of homeostasis. The paper also reviews epigenetic regulation of osteoblast differentiation via mechanisms, such as histone and DNA modifications. Additionally, we summarize the latest developments in osteoblast biology spurred by recent advancements in various modern technologies and bioinformatics. By synthesizing these insights into a comprehensive understanding of osteoblast differentiation, this review provides further clarification of the mechanisms underlying osteoblast lineage commitment, differentiation, and bone formation, and highlights potential new therapeutic applications for the treatment of bone diseases.

In Vitro Osteo-Immunological Responses of Bioactive Calcium Phosphate-Containing Urethane Dimethacrylate-Based Composites: A Potential Alternative to Poly(methyl methacrylate) Bone Cement

“…In response to HA, a subset of osteogenic cells in MSCs might transiently dedifferentiate, leading to a decrease in ALP activity during the early period tested in this study (Day3–Day7 after osteogenic induction). However, subsequent exposure to HA-containing bone composites may trigger the redifferentiation of these cells along the osteoblastic lineage, potentially leading to a more committed phenotype upon the activation of master osteogenic transcriptional factors, such as RUNX2 . This enhanced commitment may facilitate the transition of the osteoprogenitor cell to a preosteoblast state, characterized by the upregulation of markers most highly expressed during the differentiation of osteoblasts, such as ALP, COL-I, and OCN .…”

“…However, subsequent exposure to HA-containing bone composites may trigger the redifferentiation of these cells along the osteoblastic lineage, potentially leading to a more committed phenotype upon the activation of master osteogenic transcriptional factors, such as RUNX2 . This enhanced commitment may facilitate the transition of the osteoprogenitor cell to a preosteoblast state, characterized by the upregulation of markers most highly expressed during the differentiation of osteoblasts, such as ALP, COL-I, and OCN . Ultimately, these cells could differentiate into functionally mature osteoblasts, exhibiting an increased capacity for the production of mineralized deposits compared with those observed in non-HA-containing Kyphon.…”

“…48 This enhanced commitment may facilitate the transition of the osteoprogenitor cell to a preosteoblast state, characterized by the upregulation of markers most highly expressed during the differentiation of osteoblasts, such as ALP, COL-I, and OCN. 48 these cells could differentiate into functionally mature osteoblasts, exhibiting an increased capacity for the production of mineralized deposits compared with those observed in non-HA-containing Kyphon. This evidently supported that CP7 could induce mineralization via spontaneous cell-independent and cell-mediated mechanisms, both of which produced mineralization higher than that formed on Kyphon.…”