Mechanical and metabolic factors in osteoarthritis
This study determined the response of elderly human articular cartilage explants to static, cyclic or absence of mechanical load, with or without the addition of the maintenance factor IGF-1. It revealed that elderly human articular cartilage does not behave in the same way as young animal tissue, with cyclic and static loading both causing an inhibition in matrix biosynthesis. In addition, cyclic mechanical load appears to block the effects of IGF-1 in elderly human tissue, in contrast to bovine tissue in which the effects were additive. Osteoarthritic bone was found to have double the fat content of osteoporotic bone and, within the fatty acid profile, arachidonic acid was present at twice the concentration. Surprisingly, the addition of arachidonic acid to cartilage explants appeared to have no effect on matrix biosynthesis though, in retrospect, this may have been a methodological problem.
A pilot study using gene arrays revealed factors previously unidentified which may be crucial to the mechanotransduction process in chondrocytes. The considerable upregulation of transcripts for anabolic factors with no corresponding upregulation of those for matrix macromolecules raises questions about how mechanical processes regulate genes. In summary, this thesis has demonstrated that mechanical and chemokine factors interact in ways different to those found in animal cartilage. The role of fatty acids in mature human cartilage requires further investigation, but mechanically stimulated transcription of genes for anabolic factors does not appear to result in increased matrix synthesis.