Effects of cyclic tensile strain on chondrocyte metabolism: a systematic review

Abstract

Chondrocytes reorganize the extracellular matrix of articular cartilage in response to externally applied loads. Thereby, different loading characteristics lead to different biological responses. Despite of active research in this area, it is still unclear which parts of the extracellular matrix adapt in what ways, and how specific loading characteristics affect matrix changes. This review focuses on the influence of cyclic tensile strain on chondrocyte metabolism in vitro. It also aimed to identify anabolic or catabolic chondrocyte responses to different loading protocols. The key findings show that loading cells up to 3% strain, 0.17 Hz, and 2 h, resulted in weak or no biological responses. Loading between 3-10% strain, 0.17-0.5 Hz, and 2-12 h led to anabolic responses; and above 10% strain, 0.5 Hz, and 12 h catabolic events predominated. However, this review also discusses that various other factors are involved in the remodeling of the extracellular matrix in response to loading, and that parameters like an inflammatory environment might influence the biological response.

Fig 1. Schematic view of a method to stretch cell in vitro.

a: Experimental setup of a cell stretching device. The loading protocol is transferred from the computer to a vacuum pump by a control unit. The vacuum source is connected to a baseplate within an incubator, where the cell culture plates with deformable membranes are inserted hermetically sealed. b: Cross sectional view of the cell culture plates and the deformable membranes (in red) without (left) and with (right) applied vacuum. The picture on the right demonstrates the stretching of the membranes over loading posts under the influence of the vacuum. The cells are attached on the membranes and are thereby exposed to tensile strain. Inter alia, the parameters strain magnitude, frequency and loading duration can be configured.

Fig 2. Flowchart of study selection process.

Fig 3. Effects of CTS on collagen II and aggrecan mRNA levels.

Number of experiments investigating the effects of CTS on collagen II (a) and aggrecan (b) mRNA levels and summary of the effects on these parameters. Results were divided by loading duration (less than 12 h of loading, exactly 12 hours of loading, longer than 12 hours of loading) and studies were separated into: studies that found an increase in mRNA, studies that found no difference relative to control levels and studies that found a decrease of mRNA relative to control level.