Collagen biosynthesis of mechanically loaded articular cartilage explants

Objective: The purpose of this study was to investigate systematically the effect of load amplitudes, frequencies and load durations of intermittently applied mechanical pressure on the biosynthesis of collagen and non-collagenous proteins (NCP) as well as on the water content of cultured bovine articular cartilage explants. Methods: Cyclic compressive pressure was applied using a sinusoidal waveform of 0.5 Hz frequency with a peak stress of 0.1, 0.5 or 1.0 MPa for a period of 10 s followed by a load-free period of 10, 100 or 1000 s. These intermittent loading protocols were repeated for a total duration of 1, 3 or 6 days. During the final 18 h of experiments, the incorporation of [H-3]-proline into collagen and NCP, the content of water as well as the deformation of loaded explants were determined. Results: Intermittently applied, cyclic mechanical loading of articular cartilage explants consistently reduced the relative rate of collagen synthesis compared to load-free conditions. This reduced proportion of newly synthesized collagen among newly made proteins was independent of the mechanical stimuli applied. The release of newly synthesized collagen and NCP from loaded explants into the nutrient media was unaffected by any of the loading protocols applied. In addition, quantitative data are provided showing that only high amplitudes of loads and frequencies enhanced the water content of the explants. Conclusions: Previous studies reporting that osteoarthritic cartilage in vivo can synthesize elevated amounts of collagen imply that the loading protocols chosen were inadequate for simulating in vitro osteoarthritic-like alterations of collagen synthesis. In our experiments the collagen biosynthesis of chondrocytes was only minor responsive to alterations in mechanical stimuli, applied over a wide range. Thus, our results imply that the synthesis of these structural macromolecules is under the strict control of normal chondrocytes enabling them to maintain the shape of this physical demanded tissue. (c) 2005 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved.