Modeling Cell Decisions in Bone Formation

RODRIGO ASSAR; ALEJANDRO MASS; ERNESTO KOFMAN; JOAQUIN FERNANDEZ; MARTÍN A MONTECINO

Analysis, Modelling, Optimization, and Numerical Techniques

Springer

Año: 2015; p. 235 - 245

The process of bone formation involves several mechanisms, which canmanifest dysfunctions such as osteoporosis in case of imbalances between them. In basic terms, osteo-adipo progenitors derive from the bone marrow, and depending on multiple stimulus signals, can stay in their progenitor state (preosteoblast) or can differentiate to form bone and fat tissue. We point to model the dynamics of the cell decisions to differentiate from preosteoblasts to osteoblasts, considering stimulatory signals, and the important role of epigenetics. Given a cell, the presence of specific epigenetic marks favors the expression of biomarker genes and the posterior differentiation into osteoblasts. Starting with a group of marked cells, we model in silico the proliferation of such cells and the epigenetic inheritance. We consider a hybrid system  in which each cell grows continuously over time until being ready to divide, and the success in division and epigenetic inheritance includes randomness. Stimulating the proliferation of marked cells, the model predicts the dynamics to increase the number of osteoblasts helping in testing medical treatments and production in vitro.