Osteoprogenitor cell differentiation to mature bone-forming osteoblasts

Osteoblasts are the skeletal cells responsible for synthesis, deposition an d mineralization of the extracellular matrix of bone. By mechanisms that ar e only beginning to be understood, stem cells, primitive osteoprogenitors a nd related mesenchymal precursors arise in the embryo where they participat e in development of the skeleton; at least some persist in the adult organi sm, where they contribute to replacement of osteoblasts in bone turnover an d in fracture healing. However, many questions remain as to the nature of t hese precursor cell pools, including which cells constitute a stem cell poo l vs, a committed progenitor pool, which pools persist in adult life and wh ich constitute targets for hormones, cytokines, and growth factors during b one formation, turnover, and repair. During osteoprogenitor proliferation a nd differentiation, a series of cellular and molecular events occur that ar e characterized by sequential up- and downregulation of osteoblast-associat ed genes, including those for specific transcription factors, cell cycle-re lated proteins, adhesion molecules, and matrix proteins; together these res ult in a mature matrix-synthesizing osteoblast. However, the mature osteobl ast phenotype is itself heterogeneous, with subpopulations of osteoblasts e xpressing 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. (C) 20 00 Wiley-Liss, Inc.