Expression of the vitronectin receptor during embryonic development; an immunohistological study of the ontogeny of the osteoclast in the rabbit.

The development of the osteoclast during embryogenesis was studied in the rabbit by immunohistological techniques. Two monoclonal antibodies, 13C2 and 23C6, which react with the alpha-chain of the vitronectin receptor were used to define mono and multi-nucleate osteoclasts; being unreactive with other haemopoietic cells these antibodies could discriminate between osteoclasts and cells of the mononuclear phagocyte system. Staged rabbit embryos, from 14 to 28 days of age, were analysed and compared with findings from newborn and adult rabbits. No 13C2/23C6 immunoreactivity was seen in any of the tissues studied prior to day 17. 13C2/23C6-positive, mononuclear cells--presumptive osteoclast precursors--were first observed in the outer perichondrium of long-bones adjacent to the zone of hypertrophic cartilage in day 17 embryos. From day 17 onwards mono and multi-nucleate cells accumulated progressively in the perichondrium/periosteum, and by day 22 within the developing bone marrow cavity attached to bone spicules. No cells expressing the vitronectin receptor were seen at sites of embryonic or foetal haemopoiesis in yolk sac or foetal liver, that is, prior to the formation of the marrow cavity. Macrophages, defined by cross-reactivity with an antibody to human HLA-DR, first appeared in developing marrow spaces 11 days after the first osteoclast precursor appeared, suggesting that osteoclasts and definitive macrophages might develop from separate cell lineages, or that they diverge at an early stage of differentiation of haemopoietic stem cells.