The genetic transformation of bone biology

The skeleton, like every organ, has specific developmental and functional characteristics that define its identity in biologic and pathologic terms. Skeleton is composed of multiple elements of various shapes and origins spread throughout the body. Most of these skeletal elements are formed by two different tissues, cartilage and bone, and each of these two tissues has its own specific cell types: the chondrocyte in cartilage, and the osteoblast and osteoclast in bone. Finally, each of these cell types has its own differentiation pathway, physiological functions, and therefore pathological conditions. The complexity of this organ in terms of developmental biology, physiology, and pathology, along with the multitude of important conceptual advances in our understanding of skeletal biology, are such that it has become impossible to present in a short review an up-to-date summary of both cartilage and bone biology. Thus, this review will concentrate only on bone biology beyond embryonic patterning. The entire bone field is dominated by the impact of degenerative diseases, such as osteoporosis. This mere fact does influence the research in bone biology and will influence the topics presented in this review. It is no surprise that, like for most other organogenesis processes, human and mouse genetic studies have been a major driving force in redefining bone biology. Genetic studies have opened new areas of research, elucidated at the molecular level some known phenomena, and sometimes challenged untested textbook assumptions, thus transforming the field profoundly.

In mammals, bone development is a late embryonic event as it is the last event of skeleton development. Once the mesenchymal condensations prefiguring each future skeletal element have formed, between 10.5 and 12.5 days postcoitum (dpc) in mouse, they can evolve along two different paths. In some skeletal elements, prefiguring part of the skull and the clavicles, the cells of the mesenchymal condensations …