Introduction

Bone formation takes place in the organism during embryonic development, growth, remodeling, fracture repair and when induced experimentally, e.g., by the implantation of decalcified bone matrix or purified or recombinant members of the bone morphogenetic protein family. This suggests there is a large reservoir of cells in the body capable of osteogenesis throughout life. The issues addressed in this chapter are the nature of these cells in younger vs. older animals, the identification of transitional steps from stem cell to committed osteoprogenitor to osteoblast, heterogeneity of the mature osteoblast phenotype, and how differentiation may be regulated in this lineage.

Osteoblast ontogeny

Mesenchymal stem cells and multipotential and restricted progenitors

Osteoprogenitor cells reside in bone marrow stroma and in the periosteal layers of bone. They arise from multipotential mesenchymal stem cells that give rise to a number of committed and restricted cell lineages including those for osteoblasts, chondroblasts, adipocytes and myoblasts (Fig. 2.1). The fact that stem and primitive osteoprogenitors are neither morphologically nor molecularly well characterized, coupled to their low frequency, has meant that much of what we know about either class of cell has been gained through manipulations in culture. Bone marrow stromal cells grown in vitro form colonies of fibroblastic cells (colony forming unitfibroblast, CFU-F; or colony forming cell-fibroblastic, CFC-F) that, when placed in diffusion chambers and implanted into rodents, give rise to a range of differentiated cell phenotypes including osteoblasts, chondroblasts, adipocytes and fibroblasts.