INSULIN-LIKE GROWTH-FACTOR-I STIMULATES IN-VITRO MIGRATION OF PREOSTEOCLASTS ACROSS BONE ENDOTHELIAL-CELLS

Little is known about the factors and the mechanisms involved in preos teoclast emigration from the vasculature. In this study, an in vitro m odel of bone endothelial lining was mimicked by culturing bone endothe lial (BBE) cells at confluence on a 3-mu m pore polycarbonate membrane s. Preosteoclastic (FLG 29.1) cells were then added on top of the BBE cell monolayer and 10 nM insulin-like growth factor-1 (IGF-I) was adde d below the supporting membrane. Scanning and transmission electron mi croscopy were used to evaluate the chemotactic responses of preosteocl astic FLG 29.1 cells towards the ICE-I generated gradient. IGF-I poten tly stimulated chemotaxis in the FLG 29.1 cells, as shown by the migra tion of the preosteoclastic cells across the underlying BBE and throug h the intercellular junctions between adjacent endothelial cells. Subs equently, FLG 29.1 cells penetrated the pores of the supporting membra ne and reached the lower face of the membrane. Thus, IGF-I, which is a bundantly present in the bone tissue microenvironment, may play a para crine role in the recruitment of the circulating preosteoclasts from t he vascular compartment into the bone tissue. This in vitro model, whi ch mimicks the in vivo phenomenon of preosteoclast extravasation, shou ld prove useful in elucidating the molecular mechanisms that underlie this process.