Medical Evidence

Stress Fiber Analysis Of Fibroblasts Grown On Different Proteoglycans Huettinger M Institute Medical Chemistry, Vienna University, Austria

Objective: Cells building the body bearing tissue depend heavily on elements that confer mechanostability. The principle is called tensegrity. The remarkable feature thereof is that local forces cause the elements involved in mechanostability to reorient and while loosing flexibility gain stability. Intracellularly, the molecules involved are actin-filaments (stress-fibers), microtubule and intermediate filaments. They contact integrins located in the cell membrane, and so couple to the extracellular components like fibronectin, collagen and proteoglycans extending the tensegrity framework over distance. At this point a rich source of signalling is located, kinases and signal proteins, tuning production of cytokines and proteinases that coordinate tissue repair. They all are connected to the integrins receiving input of the level of mechanical stress.

Methods: We here probed the influence of proteoglycans (chondroitin sulfate) on actin filaments of fibroblasts. Confluent cultures, where cell migration is absent and tissue stability is established, were compared with cultures where mechanical disruption of the monolayer induced reorientation of the monolayer, a situation comparable to wound healing.

Results: We demonstrate by immunofluorescence microscopy that proteoglycans have minor effects on the formation of stress fibers in confluent undisturbed fibroblast cultures. There is however a dramatic effect in regenerating fibroblast monolayers on the coordinated formation of stress fibers. In the presence of chondroitin-sulfate-proteoglycan (CSPG) compared to heparan-sulfate-proteoglycan (HSPG) and dermatan-sulfate-proteoglycan (DSPG) the effect is pronounced. In addition, soluble CSPG was as effective as CSPG coupled to collagen coated on the culture dish surface. Different donor sources for the proteoglycans were studied as well. Conclusion: The data indicates that availability of CSPG for cells in the process of reconstruction supports the coordinated assembling of the structures that establish tensegrity to cells.

Source: EULAR ’98 Symposium-Satellite IBSA; Satellite Symposium 10 New approaches in OA: chondroitin sulfate (CS 4&6) not just a symptomatic treatment T.L. Vischer, B.A. Michel (Chairs) Geneva, Sept. 7th, 1998

Dr. Theo’s Comments: This study proves that chondroitin sulfate can beneficially modify cartilage tissue. This is evidence that chondroitin may be structure-modifying and not just a symptomatic treatment for osteoarthritis.