Osteopoiesis: the early development of bone cells.

An understanding of the disorders of bone formation clearly requires insights into the complex regulatory events occurring during the evolution of bone precursor cells into osteoblasts. Moreover, a rational approach to therapeutic interventions that might alter the clinical course of bone disorders must take into consideration the exact nature of the developmental control mechanism(s) being affected during the disease process. The process of osteopoiesis involves the proliferation and maturation of primitive precursor cells into functional osteoblasts. The bone cell lineage originates from mesenchymal stem cells that commit to the osteogenic cell lineage becoming osteoprogenitor cells, preosteoblasts, osteoblasts, and osteocytes. In order to understand how different regulatory signals coordinate bone cell development, it is important to study the responses of bone progenitor cells to different microenviromental signals. This requires that lineage markers be identified for the various populations of bone cells and their precursors, that cell separation techniques be established so that cells of the osteogenic lineage can be purified at different stages of differentiation, and that these isolated cells are studied under serum-free, chemically defined conditions. This review focuses on the current understanding of bone progenitor cell development, examining the various types of precursor cells, their responses to cytokines and other extracellular influences, and recent observations on the biochemical and molecular control of lineage-specific gene expression. Although the emphasis is on human cells, the importance of work using rodent cells goes without saying, and is addressed where relevant.