UNDERSTANDING BONE CELL BIOLOGY REQUIRES AN INTEGRATED APPROACH - RELIABLE OPPORTUNITIES TO STUDY OSTEOCLAST BIOLOGY IN-VIVO

The relative simplicity of all in vitro methods to study bone cell bio logy will at best result in oversimplification of the development and functional capacity of the skeleton in vivo. We have shown this to be true for selected aspects of bone cell biology, but numerous other exa mples are available. One alternative is to undertake skeletal research in vivo. It is important that those in bone research be willing to mo ve increasingly in this direction not only to understand the true comp lexitities of skeletal versatility, but also to avoid repetition and p erpetuation of erroneous or irrelevant conclusions which waste resourc es. Toward this end we have described two situations, osteopetrosis an d tooth eruption, in which reproducible abrogations or local activatio ns of bone resorption can be examined in vivo. The application of emer ging molecular and morphological techniques that permit the subcellula r dissection of metabolic pathways and their precise cellular localiza tion, such as a combination of the variety of in situ hybridization te chnologies with PCR, antisense probes, and antibody blockase, will all ow the investigator greater control of variables in vivo. We expect th at these technologies, largely worked out in vitro, combined with high ly selected, appropriate models, as we have ourlined here for osteocla st biology, will make research in vivo less intimidating and increase the frequency with which the real biology is studied directly. (C) 199 4 Wiley-Liss, Inc.