The effect of hydrostatic pressure on proteoglycan production in articular cartilage in vitro: a meta-analysis

Objective: In previous research the use of hydrostatic pressure (HP) has been applied to enhance the formation of engineered cartilage, through the up-regulation of proteoglycan synthesis by mechanotransduction. However, the HP stimulation approach has been shown to vary between studies with a wide disparity in results, including anabolic, catabolic and non-responsive outcomes. To this end, a meta-analysis of HP publications using 3D cultured chondrocytes was performed to elucidate the key experiment factors involved in achieving a mechanotransducive response. Design: The effects of different HP regimes on proteoglycan production were investigated based on the following factors: static vs dynamic application, pressure magnitude, and experiment duration. Meta-analysis was performed on raw data taken from 11 publications which employed either aggrecan gene expression analysis or dimethyl methylene blue colorimetric assay. The measure of effect was calculated based on mean difference using a random effects model. Results: Analysis revealed that a significant anabolic response was most likely achieved when the following factors were employed; a static HP application, a magnitude within the mid-high physiological range of cartilage (≤5–10 MPa) and a study duration of ≥2 weeks. Conclusions: Thus, we propose that the selection of HP experiment factors can have a significant influence on engineered cartilage development, and that the results of this meta-analysis can be used as a basis for the planning of future HP experiments.