Bones and Cartilage - Developmental Skeletal Biology

Preface

The skeleton has fascinated humankind ever since it was realized that, aside from one or several sets of genes, bare bones are our only bequest to posterity. But the skeleton is more than an articulated set of bones: its three-dimensional conformation establishes the basis of our physical appearance; its formation and rate of differentiation determine our shape and size at birth; its postnatal growth orders us among our contemporaries and sets our final stature; while its decline in later life is among the primary causes of loss of the swiftness and agility of youth. Not surprisingly, the skeleton is a central focus of many scientific and biomedical disciplines and investigations.

For the developmental or cell biologist, the skeleton provides an excellent model for studies of gene action, cell differentiation, morphogenesis, polarized growth, epithelial–mesenchymal interactions, programmed cell death, and the role of the extracellular matrix. The skeleton supplies the geneticist with a permanent record of the vicissitudes of its growth, whereby the phenotypic expression of genetic abnormalities can be studied. The orthopaedic surgeon earns a livelihood from correcting abnormalities and breaks, while the orthodontist corrects the position of teeth displaced consequent to alveolar bone dysfunction. Physiologists, biochemists and nutritionists are concerned with the skeleton’s store of calcium and phosphorus and its response to vitamins and hormones. Haematologists, on the other hand, find that the skeleton houses the progenitors of the blood cells. Pathologists endeavour to understand the disease states that result from abnormalities in skeletal cellular differentiation or function; surgeons want to prevent formation of skeletal tissues in the wounds that bear witness to their work. Vertebrate palaeontologists make their living from the analysis of the skeletons of extinct taxa. Veterinarians, physical anthropologists, radiographers, forensic scientists – the list goes on.

Bones come in all shapes and sizes. There are long bones, flat bones, curved bones, bones of irregular and geometrically indefinable shapes, large bones and small. Bones exhibit bumps, ridges, grooves, holes and depressions where they articulate with other bones, attach to tendons and ligaments, and where nerves and blood vessels course through them. Some bones and cartilages arise within the skeleton and are integral parts of it. Others arise outside the skeleton, some as sesamoids or ossifications within tendons or ligaments, others as pathological ossifications in what otherwise would be benign soft tissues. Bones and cartilages may develop during embryonic or foetal life, in larval stages or in adulthood – often late in adulthood – during normal ontogeny, wound repair, or regeneration. Bones modify themselves in response to injury, disease or parasitic infection, in the aftermath of surgery, as a defensive response to predators, as a consequence of domestication or hibernation, and through evolutionary adaptations.

My previous book on the skeleton – Developmental and Cellular Skeletal Biology – was published in 1978. That book concerned itself with how bones and cartilages are made and how these tissues, organs and systems evolved. So too does the present book, which includes and updates the earlier treatment. With respect to skeletal development, I address such questions as the following.

With respect to the evolution of skeletal tissues, organs and systems, I ask such questions as the following.

The answers to the above and many other questions may be found in this book. Sometimes the ‘answers’ are limited to descriptions. In other cases we have an extensive knowledge of the molecular, cellular, developmental and evolutionary processes involved. Some transitions (fins → limbs, for example) are understood in considerable detail, with paleontology, paleobiology, paleohistology, paleopathology, and the study of extant forms through molecular, cell and developmental biology contributing to our understanding. Other transitions – the origin of the turtle shell, for example – are much less well understood, with fossils contributing little and developmental information only beginning to appear.

Discussion of the mechanisms of skeletal development and evolution is organized into 15 parts to enable you to select with ease a topic of special interest. The range of skeletal tissues covered by the book is outlined in Part I. Although primarily devoted to bone and cartilage, Part I introduces dentine and enamel and four skeletal tissues that I call ‘intermediate’ because they display features of two or more of cartilage, bone, dentine and enamel. The four are chondroid, chondroid bone, cementum and enameloid. Discussion of these intermediate tissues is expanded in Part II in the context of what I refer to as ‘natural experiments,’ a category that includes invertebrate cartilages and an examination of the evolution of skeletal tissues.

Unusual tissues are followed in Part III by unusual modes of skeletogenesis, namely, horns, antlers, intratendinous ossifications and sesamoids, and the ossicones (knobs) of giraffes. Parts IV and V deal with the origin of skeletogenic cells, either as stem cells in embryos or adults (Chapters 10 and 11) or as more definitive skeletogenic cells (Part V). Here the emphasis is on those cells that can differentiate either as chondro- or osteoblasts (Chapter 12), on dedifferentiation as a source of skeletogenic cells in normally developing long bones and jaws and in regenerating urodele limbs (Chapters 13 and 14), and on the relationship(s) between the cells that make and the cells that break bone – osteoblasts and osteoclasts (Chapter 15).

I move explicitly into embryonic development in the three chapters in Part VI through examination of the embryonic origins of skeletogenic cells in somitic mesoderm and the neural crest, and an evaluation of the roles of epithelial–mesenchymal interactions in initiating skeletogenesis. The developmental processes that underpin skeletal formation – differentiation, morphogenesis and growth – are mediated through modification of cell division, movement, death (apoptosis) and/or specialization. To our amazement, similar genes and gene networks or pathways may be...