The in vivo and in vitro effects of bone morphogenetic protein-2 on the development of the chick mandible.

During embryonic development, neural crest derived mesenchymal (ectomesenchymal) cells in the chick mandible give rise to cartilage and membrane bone. Signaling molecules involved in the development of the mandible are less understood. To examine whether BMP-2 is involved in morphogenesis and growth of the mandible in vivo, agarose beads, loaded with BMP-2 at concentrations of 5 to 150 ng/microliter were implanted into the mandible at HH stage 22 and embryos were maintained in shell-less culture. To examine whether BMP-2 is involved in osteogenic or chondrogenic differentiation, mandibular ectomesenchyme from HH stage 22 embryos was cultured in the absence of mandibular epithelium, but in the presence of BMP-2 or BMP-2 and/or type IV collagen. Chondrogenesis and osteogenesis were examined by histological, histochemical and immunohistochemical methods. Implantation of BMP-2-containing beads in vivo retarded mandibular growth and morphogenesis in a dose-dependent manner. BMP-2 induced localized death of ectomesenchymal cells in the vicinity of the implanted bead and in proportion to the concentration of BMP-2 applied. Neither BMP-2 alone, nor BMP-2+collagen type IV, was sufficient to initiate osteogenesis in vitro in the absence of epithelium. BMP-2 inhibited chondrogenesis both in vivo and in vitro. Cartilage morphology was rod-like in the absence of BMP-2 but nodular in ectomesenchyme cultured in the presence of BMP-2. These results are discussed in relation to the stimulatory and inhibitory effects of BMPs on skeletal development.