Analyzing the effects of mechanical and osmotic loading on glycosaminoglycan synthesis rate in cartilaginous tissues

Abstract

The glycosaminoglycan (GAG) plays an important role in cartilaginous tissues to support and transmit mechanical loads. Many extracellular biophysical stimuli could affect GAG synthesis by cells. It has been hypothesized that the change of cell volume is a primary mechanism for cells to perceive the stimuli. Experimental studies have shown that the maximum synthesis rate of GAG is achieved at an optimal cell volume, larger or smaller than this level the GAG synthesis rate decreases. Based on the hypothesis and experimental findings in the literature, we proposed a mathematical model to quantitatively describe the cell volume dependent GAG synthesis rate in the cartilaginous tissues. Using this model, we investigated the effects of osmotic loading and mechanical loading on GAG synthesis rate. It is found our proposed mathematical model is able to well describe the change of GAG synthesis rate in isolated cells or in cartilage with variations of the osmotic loading or mechanical loading. This model is important for evaluating the GAG synthesis activity within cartilaginous tissues as well as understanding the role of mechanical loading in tissue growth or degeneration. It is also important for designing a bioreactor system with proper extracellular environment or mechanical loading for growing tissue at the maximum synthesis rate of the extracellular matrix.

Prediction of glycosaminoglycan synthesis in intervertebral disc under mechanical loading

“…2). The value of β has been found to be 2.41 for isolated bovine NP cells under osmotic loading (Gao et al, 2015), and this value was also found to work for both bovine NP and AF cells resided within the ECM in this studies.…”

“…This multiscale mathematical model is based on the cell volume dependent GAG synthesis theory (Gao et al, 2015) that predicts the variation of GAG synthesis rate of a cell under the influence of a mechanical stimulus, and the biphasic theory (Mow et al, 1980) that predicts the tissue deformation of IVD under mechanical loading. These two theories describe two different (biological and mechanical) phenomena at different scale levels (cell level and tissue level) were coupled together with a cell-matrix unit approach which establishes a relationship between GAG synthesis rate and local tissue dilatation.…”

“…A cell volume dependent GAG synthesis theory was adopted to model the GAG synthetic behavior of a single cell in response to mechanical stimuli (Gao et al, 2015). In this theory, it was assumed that the relative change of GAG synthesis rate (i.e., R GAG ) is proportional to the relative cell volume change (i.e., dilatation), and there is an optimal cell volume corresponding to the maximum GAG synthesis rate, mathematically, $$\frac{R^{GAG}}{R_0^{GAG}}=1-\beta true\mid \frac{V^{cell}-V_0^{cell}}{V_0^{cell}}true\mid ,$$ where $R_0^{GAG}$ is the maximum GAG synthesis rate, V and $R_0^{cell}$ are the cell volumes at current and optimal state, respectively, and β is a positive parameter characterizing the effect of cell volume change on GAG synthesis rate and it was assumed to be independent of cell volume in this study.…”

“…Recently, we have developed a cell volume dependent GAG synthesis theory to characterize the cell biosynthetic behavior in response to mechanical stimuli (Gao et al, 2015). The theory is based on the hypothesis that the change of cell volume is a regulator for downstream posttranslational biosynthesis (Guilak et al, 1995; O'Conor et al, 2014; Wong et al, 1997).…”

“…The deviation of cell volume from its optimal state was considered as a mechanical stimulus, and it was correlated with the reduction (or decrease) of GAG synthesis rate from its maximum value. This theory has been shown to be able to predict GAG synthesis rate of isolated intervertebral disc cells under different osmotic loading conditions (Gao et al, 2015). However, there is no mathematical model available to quantify the variation of GAG synthesis rate within the disc in response to the externally applied mechanical load.…”