Advances in the osteoblast lineage

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 and primitive osteoprogenitors and related mesenchymal precursors arise in the embryo and at least some appear to persist in the adult organism, where they contribute to replacement of osteoblasts in bone turnover and in fracture healing. In this review, we de scribe the morphological, molecular, and biochemical criteria by which oste oblasts are defined and cell culture approaches that have helped to clarify transitional stages in osteoblast differentiation. Current understanding o f differential expression of osteoblast-associated genes during osteoprogen itor proliferation and differentiation to mature matrix synthesizing osteob lasts is summarized. Evidence is provided to support the hypothesis that th e mature osteoblast phenotype is heterogeneous with subpopulations of osteo blasts expressing only subsets of the known osteoblast markers. Throughout this paper, outstanding uncertainties and areas for future investigation ar e also identified.