Cellular scale model of growth plate: An in silico model of chondrocyte hypertrophy

• Published in: Journal of theoretical biology Vol. 428; pp. 87 - 97
• Main Authors: Castro-Abril, H.A., Guevara, J.M., Moncayo, M.A., Shefelbine, S.J., Barrera, L.A., Garzón-Alvarado, D.A.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 07.09.2017
• Subjects: Biomechanical Phenomena; Cell Differentiation - drug effects; Chondrocytes - drug effects; Chondrocytes - pathology; Compressive Strength - drug effects; Computer Simulation; Growth Plate - pathology; Hedgehog Proteins - pharmacology; Hypertrophy; Models, Biological; Parathyroid Hormone-Related Protein - pharmacology; Tensile Strength - drug effects; Time Factors; Weight-Bearing
• ISSN: 0022-5193; 1095-8541
• DOI: 10.1016/j.jtbi.2017.05.015

•First approach to understanding the combined effects of biochemical and mechanical stimuli on the hypertrophy process of chondrocytes during endochondral ossification•Short term effects of mechanical loading and biochemical regulation (Ihh-PTHrP loop) on chondrocytes behavior•Results show high resemblance with the observed in vivo hypertrophy process•In absence of either Ihh or PTHrP molecules, premature hypertrophy is observed The growth plate is the responsible for longitudinal bone growth. It is a cartilaginous structure formed by chondrocytes that are continuously undergoing a differentiation process that starts with a highly proliferative state, followed by cellular hypertrophy, and finally tissue ossification. Within the growth plate chondrocytes display a characteristic columnar organization that potentiates longitudinal growth. Both chondrocyte organization and hypertrophy are highly regulated processes influenced by biochemical and mechanical stimuli. These processes have been studied mainly using in vivo models, although there are few computational approaches focused on the rate of ossification rather than events at cellular level. Here, we developed a model of cellular behavior integrating biochemical and structural factors in a single column of cells in the growth plate. In our model proliferation and hypertrophy were controlled by biochemical regulatory loop formed between Ihh and PTHrP (modeled as a set of reaction-diffusion equations), while cell growth was controlled by mechanical loading. We also examined the effects of static loading. The model reproduced the proliferation and hypertrophy of chondrocytes in organized columns. This model constitutes a first step towards the development of mechanobiological models that can be used to study biochemical interactions during endochondral ossification.