Cartilage mechanobiology: The effects of loading on the fine structure and function of chondroitin sulfate glycosaminoglycans

Chondroitin sulfate is a critical component of articular cartilage due to its contribution to the tissue's resistance to compressive deformation. Alterations in the biosynthesis of this molecule over time could impact the ability of the tissue to perform its necessary functions. Several factors have been shown to alter the biosynthesis of chondroitin sulfate in cartilage; among them are age, disease, depth of tissue, and mechanical compression. Specifically, mechanical compression has been shown to have a significant effect on the sulfation pattern and chain length and number in cartilage explant studies. The mechanisms that govern these alterations, however, have not been determined. The purpose of this study is to examine the effects of mechanical compression on chondroitin sulfate biosynthesis and analyze the roles of two possible mechanisms; enzyme transcription and organelle deformation.

The effects of mechanical compression on the transcription rates of enzymes associated with the biosynthesis of chondroitin sulfate have not been previously studied. To perform this study in a bovine model, portions of the bovine genome had to be sequenced, PCR primers designed, and bulk expression levels determined. Static compression resulted in the significant up-regulation of two genes of interest: chondroitin sulfate and GalNAc 4S,6-sulfotransferase. Dynamic compression resulted in the significant up-regulation of the three sulfotransferases responsible for the bulk of sulfation in cartilage tissue. These results indicate a transient mechanotransduction reaction that differs based on the load regime.

The effect of mechanical loading on the biosynthesis of chondroitin sulfate has been studied previously, however, this study seeks to examine more comprehensive loading regimes. Static compression and release resulted in an increase in 6-sulfation and a decrease in 4-sulfation that lasted to 48 hours after release of compression. Dynamic compression and release had the opposite effect on sulfation ratio, with an increase in 4-sulfation compared to 6-sulfation. The transcription changes seen in this study do not indicate the changes that occur in the end products of synthesis. Other factors may play a larger role, such as precursor availability or transport through the Golgi apparatus.

Intracellular organelles react to static compression of the surrounding tissue in one of two manners. The majority of organelles deform much as the nucleus, proportionally in volume and shape to the cell. (Copies available exclusively from MIT Libraries, Rm. 14-0551, Cambridge, MA 02139-4307. Ph. 617-253-5668; Fax 617-253-1690.) (Abstract shortened by UMI.)