Secondary ossification centers evolved to make endochondral bone growth possible under the weight-bearing demands of a terrestrial environment

The growth of long bones occurs in narrow discs of cartilage, called growth plates that provide a continuous supply of chondrocytes subsequently replaced by newly formed bone tissue. These growth plates are sandwiched between the bone shaft and a more distal bone structure called the secondary ossification center (SOC). We have recently shown that the SOC provides a stem cell niche that facilitates renewal of chondro-progenitrors and bone elongation. However, a number of vertebrate taxa, do not have SOCs, which poses intriguing questions about the evolution and primary function of this structure. Evolutionary analysis revealed that SOCs first appeared in amniotes and we hypothesized that this might have been required to meet the novel mechanical demands placed on bones growing under weight-bearing conditions. Comparison of the limbs of mammals subjected to greater or lesser mechanical demands revealed that the presence of a SOC is associated with the extent of these demands. Mathematical modelling with experimental validation showed that the SOC reduces shear and normal stresses within the growth plate; while relevant biological tests revealed that the SOC allows growth plate chondrocytes to withstand a six-fold higher load before undergoing apoptosis. Hypertrophic chondrocytes, the cells primarily responsible for bone elongation, were the most sensitive to loading, probably due to their low Youngs modulus (as determined by atomic force microscopy). Our present findings indicate that the primary function of the evolutionary delineation of epiphyseal cartilage into spatially separated growth plates was to protect hypertrophic chondrocytes from the pronounced mechanical stress associated with weight-bearing in a terrestrial environment.