The cartilage extracellular matrix as a transient developmental scaffold for growth plate maturation

The cartilage growth plate is a specialized developmental tissue containing characteristic zonal arrangements of chondrocytes. The proliferative and differentiative states of chondrocytes are tightly regulated at all stages including the initial limb bud and rudiment cartilage stages of development, the establishment of the primary and secondary ossification centers, development of the growth plates and laying down of bone. A multitude of spatio-temporal signals, including transcription factors, growth factors, morphogens and hormones, control chondrocyte maturation and terminal chondrocyte differentiation/hypertrophy, cell death/differentiation, calcification and vascular invasion of the growth plate and bone formation during morphogenetic transition of the growth plate. This involves hierarchical, integrated signaling from growth and factors, transcription factors, mechanosensory cues and proteases in the extracellular matrix to regulate these developmental processes to facilitate progressive changes in the growth plate culminating in bone formation and endochondral ossification. This review provides an overview of selected components which have particularly important roles in growth plate biology including collagens, proteoglycans, glycosaminoglycans, growth factors, proteases and enzymes.