Regulation of osteogenic differentiation during skeletal development

Abstract

Bone formation during skeletal development involves a complex coordination among multiple cell types and tissues. Bone is of crucial importance for the human body, providing skeletal support, and serving as a home for the formation of hematopoietic cells and as a reservoir for calcium and phosphate. Bone is also continuously remodeled in vertebrates throughout life. Osteoblasts and osteoclasts are specialized cells responsible for bone formation and resorption, respectively. Early development of the vertebrate skeleton depends on genes that control the distribution and proliferation of cells from cranial neural crest, sclerotomes, and lateral plate mesoderm into mesenchymal condensations, where cells differentiate to osteoblasts. Significant progress has been made over the past decade in our understanding of the molecular framework that controls osteogenic differentiation. A large number of morphogens, signaling molecules, and transcriptional regulators have been implicated in regulating bone development. A partial list of these factors includes the Wnt/beta-catenin, TGF-beta/BMP, FGF, Notch and Hedgehog signaling pathways, and Runx2, Osterix, ATF4, TAZ, and NFATc1 transcriptional factors. A better understanding of molecular mechanisms behind osteogenic differentiation would not only help us to identify pathogenic causes of bone and skeletal diseases but also lead to the development of targeted therapies for these diseases.

Human Serine Protease HTRA1 Positively Regulates Osteogenesis of Human Bone Marrow-derived Mesenchymal Stem Cells and Mineralization of Differentiating Bone-forming Cells Through the Modulation of Extracellular Matrix Protein

“…A complex molecular network of signaling pathways and regulatory factors governs the osteogenesis of multipotent MSCs [17,18,27], being reliant on the activation and regulation of a number of key molecular targets including RUNX2, ALP, SPP1, and IBSP [28]. Although there have been significant advances in our understanding of the molecular mechanisms involved in controlling osteogenic differentiation, the influence of serine proteases on such processes remains relatively obscure.…”

Osteogenic BMPs promote tumor growth of human osteosarcomas that harbor differentiation defects

“…2,3 Mesenchymal stem cells (MSCs) are adherent bone marrow stromal cells that can differentiate into osteogenic, chondrogenic, adipogenic, and myogenic lineages. [17][18][19][20][21] Osteoblastic differentiation of MSCs is an essential process of bone formation, [17][18][19][20] and is tightly regulated. 20,21 BMPs play an important role in osteoblast differentiation.…”

“…[17][18][19][20][21] Osteoblastic differentiation of MSCs is an essential process of bone formation, [17][18][19][20] and is tightly regulated. 20,21 BMPs play an important role in osteoblast differentiation. 20,[22][23][24] We have analyzed the osteogenic potential of 14 human BMPs and found that BMP-2, 6, 9 are the most potent inducers of osteogenic differentiation both in vitro and in vivo.…”

Constitutive Activation of Smoothened Leads to Impaired Developments of Postnatal Bone in Mice

“…Among various regulatory factors, Runx2 is an essential transcription factor for osteoblast differentiation and bone formation (Deng et al, 2008;Franceschi et al, 2007). Runx2 is considered to induce chondrocyte maturation and enhance chondrocyte proliferation through the direct induction of Ihh expression in the growth plate (Shimoyama et al, 2007).…”