The most prevalent degenerative joint condition, osteoarthritis, affects 22 percent of individuals over the age of 40 worldwide. The molecular changes associated with osteoarthritis are still unknown, despite substantial medical studies on the disease. In a recent study, scientists used several tools to monitor the development of the disease and the changes it causes. The smooth surface of cartilage in joints, along with a lubricant called synovial fluid, helps them resist weight-bearing activities. Several chemicals are present in the fluid, including phospholipids and hyaluronan (HA). Researchers have tried to identify early stages of joint disease by monitoring the molecular weight and concentration of HA because the cartilage environment cannot be easily repaired or regenerated.
“Although we know there is very little friction in healthy joints, it is not clear which other molecules are involved and how they change during osteoarthritis,” said Donald Biggar Willett Faculty Scholar and Rosa Espinosa Professor of Environmental Engineering. Margel (EIRH) said. and science, and materials science and engineering. “During the early stages of osteoarthritis, cartilage begins to erode, and previous research has shown that the molecular composition of the synovial fluid changes. We wanted to see if the two changes were related.”
In a healthy joint, the molecular weight of HA is between 2–20 Mda and the concentration is between 1–4 mg/ml. However, in diseased joints, HA breaks down resulting in reduced molecular weight. Along with this, its concentration also decreases ten times. Building on these observations by other researchers, the study looked at how the concentration and molecular weight of HA affected the structure of healthy and diseased joints.
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To do this, the researchers incubated vesicles with high and low molecular weight HA. Using neutron scattering and light scattering, they found that the molecular weight of HA can substantially change the structure of the vesicles. Low molecular weight HA, which mimics osteoarthritis-diseased joints, results in larger vesicle size. They also observed that the molecular weight of HA alters the thickness of the phospholipid layers at the joints.
The researchers also studied how these differences might affect the formation of a protective film; In joints, this film is responsible for the very low friction required for smooth motion. Once again, they used a combination of techniques, quartz crystal microbalance and atomic force microscopy, to investigate how these molecules assemble on gold surfaces. “Formation of a film is possible only when there is an optimal concentration of HA and phospholipids. Although gold surfaces bear little resemblance to cartilage, our study indicates that there may be an optimal concentration even under biological conditions,” Espinosa Margel said. “This is an important observation because we can use the concentration changes as a diagnostic tool.”
“We are at a point where you need to use multiple techniques on a complex system like this,” said Mark Rutland, professor of surface science at the KTH Royal Institute of Technology. “None of these techniques alone would have given us any information. The key thing was to see all the different effects and put the pieces together to show that the molecular weight of HA had a huge effect on the characteristics of that layer.” phospholipids that form with it.”
The researchers are now working on using cartilage to understand whether their observations with gold surfaces also hold true in a biologically relevant system. He is also interested in studying other molecular components found in joints to create a more comprehensive model of the changes associated with osteoarthritis.