Osteoprogenitor cell differentiation to mature bone-forming osteoblasts

Abstract

Osteoblasts are the skeletal cells responsible for synthesis, deposition and mineralization of the extracellular matrix of bone. By mechanisms that are only beginning to be understood, stem cells, primitive osteoprogenitors and related mesenchymal precursors arise in the embryo where they participate in development of the skeleton; at least some persist in the adult organism, where they contribute to replacement of osteoblasts in bone turnover and in fracture healing. However, many questions remain as to the nature of these precursor cell pools, including which cells constitute a stem cell pool vs. a committed progenitor pool, which pools persist in adult life and which constitute targets for hormones, cytokines, and growth factors during bone formation, turnover, and repair. During osteoprogenitor proliferation and differentiation, a series of cellular and molecular events occur that are characterized by sequential up- and downregulation of osteoblast-associated genes, including those for specific transcription factors, cell cycle-related proteins, adhesion molecules, and matrix proteins; together these result in a mature matrix-synthesizing osteoblast. However, the mature osteoblast phenotype is itself heterogeneous, with subpopulations of osteoblasts expressing only subsets of the known osteoblast markers, raising intriguing questions, including how different pools of osteoblasts or their precursors may respond to therapeutic agents. Drug Dev. Res. 49:206–215, 2000. © 2000 Wiley-Liss, Inc.