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 (ectome senchymal) cells in the chick mandible give rise to cartilage and memb rane bone. Signaling molecules involved in the development of the mand ible are less understood. To examine whether BMP-2 is involved in morp hogenesis and growth of the mandible in vivo, agarose beads, loaded wi th BMP-P at concentrations of 5 to 150 ng/mu l were implanted into the mandible at HH stage 22 and embryos were maintained in shell-less cul ture. To examine whether BMP-2 is involved in osteogenic or chondrogen ic differentiation, mandibular ectomesenchyme from HH stage 22 embryos was cultured in the absence of mandibular epithelium, but in the pres ence of BMP-2 or BMP-2 and/or type IV collagen. Chondrogenesis and ost eogenesis were examined by histological, histochemical and immunohisto chemical methods. Implantation of BMP-2-containing beads in vivo retar ded mandibular growth and morphogenesis in a dose-dependent manner. BM P-2 induced localized death of ectomesenchymal cells in the vicinity o f the implanted bead and in proportion to the concentration of BMP-2 a pplied. Neither BMP-2 alone, nor BMP-2+collagen type IV, was sufficien t to initiate osteogenesis in vitro in the absence of epithelium. BMP- 2 inhibited chondrogenesis both in vivo and in vitro. Cartilage morpho logy was rod-like in the absence of BMP-S but nodular in ectomesenchym e cultured in the presence of BMP-2. These results are discussed in re lation to the stimulatory and inhibitory effects of BMPs on skeletal d evelopment.