The skeleton from start to finish

The Skeleton is a comprehensive review of the field of skeletal developmental biology. As the title suggests, individual chapters address the biochemistry, genetics and molecular biology of six major aspects of bone growth: (i) chondrogenesis and cartilage; (ii) skeletal development; (iii) regulation of osteoblasts; (iv) bone modeling and remodeling; (v) bone mineralization and (vi) skeletal dysmorphologies. Broadly speaking, the first half of the book covers bone and cartilage microstructure, and the second half addresses macrostructure.The book begins with a discussion of the growth and regulation of cartilage, with topics ranging from the formation of the initial condensation to the effect of mechanotransduction on cartilage. A particularly interesting chapter by Hackenmiller et al. describes the tremendous potential of post-translational modification for altering the activity of bone morphogenetic proteins (BMPs) and the wingless (Wnt) and hedgehog genes. Subsequent sections review the major genes and growth factors involved in skeletal development and osteoblast activity. The chapters on the control of skeletogenesis focus on retinoids, the homeobox and hedgehog gene families, Wnt, fibroblast growth factors (FGFs) and BMPs, and chapters on osteoblast and osteoclast differentiation concentrate on osteogenic protein-1 (OP-1), osterix (osx), runt-related transcription factor 2 (Runx2, also known as Cbfa1), and the transforming growth factor-β (TGF-β) superfamily. Topics relating to bone macrostructure include the regulation of endochondral growth, trabecular remodeling, and the effects of microgravity on bone remodeling. A small section on bone mineralization covers the growth of bone crystals, fetal bone mineralization and homeostasis, and the pleiotropic effects of Vitamin D on osteoblasts and the extracellular matrix. The final clinically focused chapters on skeletal dysmorphologies, including facial clefting, achondroplasia and hypochondroplasia, and the effects of toxins on fetal skeletal development also highlights the normal functions of genes involved.Two particularly noteworthy chapters explain the complexity of the interaction between the regulation of cartilage and bone development. Takeda et al. report that Cbfa1, a well-known mediator of osteoblast differentiation, also regulates the differentiation of hypertrophic chondrocytes via Indian hedgehog (Ihh). In the chapter by Pacifici et al. intramembranous bone formation adjacent to the growth plate is shown to be induced by Ihh. These chapters suggest a ‘role reversal’ during endochondral bone growth, with Cbfa1 upstream of Ihh during chondrogenesis but downstream of Ihh during osteogenesis. As Pacifici et al. point out, the signaling pathways of cartilage and bone development are intricately related in many ways. Several of the chapters emphasize that the same genes and growth factors that are crucial for bone development are also involved in the development of many other tissues. However, some mention of other mechanisms affecting skeletal growth, such as epigenetic interactions between physiological processes and external stimuli, would be useful to the reader.Overall, the contributions in this volume are sufficiently varied to include many of the primary research areas in skeletal biology, including the major genetic and biochemical pathways involved in both cartilage and bone growth. This diversity makes the book a useful reference for readers seeking a concise refresher about molecular and genetic aspects of skeletogenesis. There is considerable repetition in the introductions to many chapters, which is frustrating when reading the whole book, but does allow individual chapters to stand alone as references or as reading assignments. Although timeliness is always a challenge in edited volumes, this book includes references as recent as 2003, making it a suitable resource for researchers and students alike. The Skeleton will therefore be useful for developmental biologists, clinicians and others for whom understanding skeletal developmental biology is important.