Transcription in the Osteoblast: Regulatory Mechanisms Utilized by Parathyroid Hormone and Transforming Growth Factor-Beta

Christine E. Boumah, Nagarajan Selvamurugan, Nicola C. Partridge

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

The osteoblast is a cell of mesenchymal origin sharing a common progenitor stem cell with chondrocytes, myoblasts, and bone marrow stromal cells including adipocytes. Preosteoblasts, however, are capable of responding to a variety of extracellular signaling pathways and further differentiating into bone-lining mature osteoblasts and osteocytes; this process of osteoblast differentiation or osteogenesis, crucial for skeletal tissue formation, repair, and maintainance, is under extensive investigation. Osteoblast differentiation is often subdivided into three stages: (1) a proliferation stage, during which the cells exit from the cell cycle and fully commit to the osteoblast phenotype; in this stage, the osteoblasts express high levels of immediate early genes (c-fos, c-jun, c-myc), histones, cyclins, and several other genes specific to proliferating cells (1-3); (2) a growth arrest stage, accompanied by development and maturation of extracellular matrix, downregulation of growth-associated genes, and expression of high levels of alkaline phosphatase and collagen (4, 5); and (3) a mineralization stage, with maximal osteoblastic expression of extracellular matrix components including noncollagenous bone matrix proteins such as osteocalcin, osteopontin, and bone sialoprotein (4, 6, 7). Osteoblast differentiation and the mechanisms responsible for the temporal and sequential display of distinct subsets of transcriptionally active osteoblastic genes were established using in vitro osteoblast culture models and, more recently, in in vivo studies with mice. Osteoblast activities are regulated, in a stage-specific manner, by hormones including parathyroid hormone (PTH) (8, 9), 1,25(OH)2 vitamin D3 (10), estrogen (11, 12), and glucocorticoids (13, 14). Osteoblast differentiation is also regulated by cytokines and various local factors such as transforming growth factor-beta (TGF-β) (15, 16) and fibroblast growth factor (17).

Original languageEnglish (US)
Title of host publicationProgress in Nucleic Acid Research and Molecular Biology
EditorsKivie Moldave
Pages287-321
Number of pages35
DOIs
StatePublished - 2005

Publication series

NameProgress in Nucleic Acid Research and Molecular Biology
Volume80
ISSN (Print)0079-6603

ASJC Scopus subject areas

  • Molecular Biology

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