Timing of resting zone parathyroid hormone-related protein expression affects maintenance of the growth plate during secondary ossification: a computational study

Abstract

Secondary ossification and maintenance of the growth plate are crucial aspects of long bone formation. Parathyroid hormone-related protein (PTHrP) has been implicated as a key factor in maintaining the growth plate, and studies suggest that PTHrP expression in the resting zone is closely related with formation of the secondary ossification center (SOC). However, details of the relationship between resting zone PTHrP expression and preservation of the growth plate remain unclear. In this study, we aim to investigate the role of resting zone PTHrP expression on maintenance of the growth plate using a computational method. We extend an existing continuum-based particle model of tissue morphogenesis to include PTHrP and Indian hedgehog (Ihh) signaling, allowing the model to capture biochemical and mechanical regulation of individual cell activities. Our model indicates that the timing of resting zone PTHrP expression --specifically the rate of increase in production at the onset of SOC formation-- is potentially a crucial mechanism for maintenance of the growth plate.