Cell proliferation and specialization during endochondral osteogenesis in young rats.

Endochondral osteogenesis was studied autoradiographically in ribs and tibiae of 32 Long-Evans rats injected with 1 microc/gm H(3)-thymidine at 6 days of age and sacrificed at intervals between 1 hour and 2 weeks later. Proliferation and specialization of bone cells were studied by analyses of (a) the percentage of mitoses which were labeled, (b) the percentage of labeled nuclei in bone cells, and (c) grain counts. The following conclusions were derived: The various types of bone cells represent different functional states of the same cell. Cell division is usually restricted to cells in the morphologically unspecialized "osteoprogenitor" state. Specialized bone cells arise by modulation of osteoprogenitor cells. The average cell generation time is shortest in the metaphysis, longest in the periosteum, and intermediate in the endosteum. The average duration of DNA synthesis is relatively constant (about 8 hours). With increasing length of generation time there is a slight increase in G(2) + mitosis, but the major change is a lengthening of G(1). After dividing, cells in the osteoprogenitor state may remain within the progenitor pool or undergo modulation of cell type, specializing as osteoblasts or becoming incorporated in osteoclasts.