Osteoarthritis is the most common degenerative joint disease, affecting 22 percent of adults over 40 globally. Although the condition has been extensively studied through a medical perspective, the molecular changes associated with osteoarthritis remain unclear. In a new study, researchers have used a combination of techniques to track the progression of the changes associated with the condition.
In healthy joints, the cartilage in the joints, and the lubricating synovial fluid, provide a smooth surface that helps withstand weight-bearing movements. The fluid contains several molecules, including hyaluronan (HA) and phospholipids. Since the cartilage environment cannot be quickly healed or repaired, researchers have tried to diagnose the early stages of joint disease by monitoring the molecular weight and concentration of HA.
“Although we know that in healthy joints there is very low friction, it is unclear which other molecules are involved and how they change during osteoarthritis,” said study co-author Rosa Espinosa-Marzal. “During the early stages of osteoarthritis, cartilage starts degrading, and previous research has shown that the molecular composition of the synovial fluid changes. We wanted to see if the two changes are related to each other.”
In a healthy joint, the molecular weight of HA varies between 2-20 MDa with a concentration ranging from 1-4 mg/ml. However, in joints with osteoarthritis, HA is broken down resulting in a lower molecular weight. Additionally, its concentration is also reduced by 10 times.
Based on these observations, made by prior researchers, the study looked at how the concentration and molecular weight of HA influences the structure of healthy and diseased joints. The team combined vesicles with high and low molecular weight HA; lower molecular weight HA, which mimics osteoarthritic joints, results in larger vesicle size.
Using neutron scattering and light scattering, they discovered that the molecular weight of HA can vastly change the structure of the vesicles. They also observed that the molecular weight of HA changes the thickness of the phospholipid layers in the joints.
The researchers also studied how these differences can influence the formation of a protective film; in joints this film is responsible for the very low friction we need for unhindered motion.
Once again, they used a combination of techniques, quartz crystal microbalance and atomic force microscopy, to examine how these molecules assemble on gold surfaces. “The formation of a film is possible only when there is an optimal concentration of HA and phospholipids. Even though the gold surfaces have very little in common with cartilage, our studies indicate that there could also be an optimum concentration under biological conditions,” Espinosa-Marzal said.
She noted that this observation allows for the concentration changes to be used as a diagnostic tool. “We are at a point where you need to use multiple techniques on a complex system like this,” said study co-author Mark Rutland.
“None of these techniques alone would have given us any insight. The key was to look at all the different effects and put the pieces together to show that the molecular weight of HA has a huge effect on the characteristics of the layer that is formed with phospholipids.”
The researchers are planning to study the other molecular components found in joints in an effort to build a more comprehensive model of the changes associated with osteoarthritis.
Reference:
Sun K, et al, “Insight into the assembly of lipid-hyaluronan complexes in osteoarthritic conditions”. Biointerphases, 2023; 18 (2) DOI: 10.1116/6.0002502.
