Mechanical loading regimes affect glucose and lactate metabolism of chondrocytes

Normally, articular cartilage functions well over a lifetime, but traumatic injury or the degenerative changes associated with osteoarthritis can result in significant erosion of the articular layer. The poor intrinsic repair capacity of chondrocytes restricts the process of cartilage tissue formation and creates a demand for tissue engineered cartilage. To cope with all the challenging demands of cartilage tissue engineering, control of the tissue engineering proces is needed. Hence, a sophisticated bioreactor is required. The bioreactor, which is used in this study, can stimulate constructs using direct compression and perfuse them for supply of nutrients and removal of waste products. Chowdhurry et al. 4 showed that it is possible to modulate chondrocyte metabolism (e.g. proliferation or extracellular matrix (ECM) synthesis) by mechanical stimulation. The largest differences were seen between 12 hours (I12) and 1.5 hours (I1.5) of intermittent loading. Now that it is possible to direct the cells to different metabolic processes, the next step for tissue engineering is to investigate a way to control these processes. It is known that glucose can be used for energy supply or for glycosaminoglycan synthesis and that in those processes the production of lactate is different. It is hypothesized that the energy metabolism is different when the cells are proliferating or synthesizing ECM. Hence, the aim of this study is to stimulate chondrocyte/agarose constructs with the two intermittent loading regimes (I12, I1.5), in order to stimulate proliferation or ECM synthesis, and analyse whether or not the glucose consumption and/or lactate production are different. It is demonstrated the chondrocytes subjected to different dynamic loading regimes have different rates of glucose consumption and lactate production. The I12 group consumed glucose and produced lactate at a lower rate, than the controls and the I1.5 group. It is shown that the use of the ratio of produced lactate over consumed glucose, indicates differences between controls and the I12 and I1.5 groups. In addition, differences in DNA content and GAG production between the I12 and I1.5 groups are found. Of major importance in the latter issue is the fact that apparently similar stimulation protocols between the latter study and the study of Chowdhurry et al. 4 show opposite effects in proliferation and ECM synthesis. The combined results indicate that the energy metabolism is different when the cells are either proliferating or synthesizing ECM. Measuring chondroycte metabolism is concluded to be a promising tool to monitor cartilage TE, although …