Study characterizes protein filament’s role in cartilage strength

The protein filament vimentin provides healthy cartilage with the mechanical strength and flexibility necessary to resist stress, according to a study published in the Journal of Orthopaedic Research.

The study offers the first detailed look at the role of vimentin in cartilage in both healthy and osteoarthritic joints. It opens the door to the possibility that new treatments blocking vimentin disruption could slow osteoarthritis (OA) and reduce hip or knee replacement surgeries, according to a press release.

“We have shown for the first time that vimentin plays a big role in helping cells handle mechanical stress in cartilage,” Dominik R. Haudenschild, PhD, a lead author of the study, stated in the release. “This has important implications for understanding why cartilage breaks down during osteoarthritis and holds potential for developing treatments that prevent filament damage.”

Methods and findings

Haudenschild embedded human cartilage cells from healthy and osteoarthritic knee joints into a gel that allowed precise measurement of changes in cellular dimensions while the cells underwent mechanical compression. In some cases, cells were first treated with a chemical that specifically caused the vimentin to break down while leaving other protein filaments unaffected.

According to the findings, vimentin in normal chondrocytes formed an inner cage-like network noted as being “substantially stiffer” and contributing significantly to overall cellular stiffness. Disruption of vimention was found to reduce stiffness approximately 2.8-fold in normal chondrocytes, while osteoarthritic chondrocytes were less stiff and affected by vimentin disruption, which the authors note could have occurred because the disease process was already under way. The authors noted that this finding indicated potential treatments targeting vimentin disruption must be delivered early in the course of OA before vimentin breakdown has occurred.

Further work

“Healthy vimentin appears to be critical in maintaining cartilage’s vitality,” Haudenschild stated in the release. “Blocking its breakdown early in the disease process or restoring its structure in osteoarthritic cells to look more like it does in healthy cells could be promising avenues of treatment.”

Using a combination of fluorescent proteins and live-cell imaging on a confocal microscope, the team also obtained some of the highest-resolution 3-D images of vimentin in chondrocytes ever produced. The images confirmed the lab results by revealing that vimentin filaments form a tight cage within normal cartilage cells, keeping them stiff and stable.

Haudenschild’s group is working on further research to help determine the role of vimentin in arthritis and aging. The investigators are looking at the biochemical aspects of the issue and utilizing computer modeling techniques.

Reference:
Haudenschild DR. J Orthop Res. 2011. doi:10.1002/jor.21198.

Follow ORTHOSuperSite.com on Twitter