13 Extracellular Matrix in the Skeleton

The extracellular matrix (ECM) is a highly heterogeneous amalgam of multidomain molecules that are intimately involved in the development, growth, function, and homeostasis of every organ system, including the skeleton. Similar to other connective tissues, bone and cartilage matrices consist of collagens, proteoglycans (PGs), and noncollagenous (NC) proteins, in addition to including enzymes involved in matrix assembly and degradation. That the vast majority of these molecules are also found in other tissues indicates that relative differences in ECM composition specify form and function at discrete anatomical locations of the developing and adult skeleton. This chapter provides an introduction to ECM composition and organization in the skeleton, and a brief review of the contribution of selected matrix molecules to bone formation and remodeling that is mostly based on genetic evidence from loss-of-function studies in mice. Similar topics are also covered in other chapters of this book, and a number of excellent reviews are available that describe various aspects of ECM biology in greater detail. ECM COMPOSITION AND ORGANIZATION Collagens Collagens are the most abundant and diverse components of the connective tissue (Mecham 1998; Birk and Bruckner 2005). All collagens possess at least one triple helical (or collagenous [COL]) domain and NC domains of variable length and composition. Most collagens give rise to morphologically diverse suprastructures that are also referred to as molecular composites because they include additional collagens and NC proteins (Birk and Bruckner 2005). For example, tissue-specific organization of collagen I or II networks is largely regulated by copolymerization with...