The researchers say the finding offers the strongest evidence yet that treatments designed to increase levels of lubricin in humans may help stall the deterioration of arthritic joints.
The team found that the arthritic joints of mice lacking the gene that controls the production of lubricin show greater friction than do joints in normal animals. When observed at the molecular level, the surface of the mutant animals' joint cartilage also appears rougher and less stiff -- a finding that the researchers said suggests a loss of the cartilage's mechanical integrity without lubricin.
"Lubricin has been considered important, but the experiments had not been done," said Stefan Zauscher, a professor of mechanical engineering and materials science at the Pratt School. "This is the first look at the effects on biomechanics of lubricin's presence or absence."
Team member Jeffrey Coles, a Ph.D. student working in Zauscher's laboratory, presented the findings on Monday, Feb. 12, at the annual meeting of the Orthopaedic Research Society, in San Diego. The work was supported by the National Institutes of Health.
While lubricin had been suspected to play a role in reducing joint friction, earlier studies had focused on another constituent of joint fluid called hyaluronic acid. Injections of this material are frequently used as a treatment for osteoarthritis, the most common form of arthritis. However, the treatment seems to work primarily as an anti-inflammatory agent, Zauscher noted, doing little to prevent further joint damage.
Last year, Zauscher's group reported evidence that lubricin acts as a repellant boundary layer between joint surfaces, reducing friction by preventing contacts altogether rather than simply "greasing the wheels" http://www.pratt.duke.edu/news/index.php?story=260.
Those results stemmed from the first examination of the changing molecular forces between a model joint and glass slide as the amount of lubricin in the solution between them increased.
Now, the researchers have applied a similar technique to the molecular-level study of mouse joints, comparing normal mice to those lacking the gene for lubricin. They used an atomic force microscope (AFM) to examine the cartilage found on the surface of the ball at the top of the thigh bone that fits into the hip socket of the mice.
AFM microscopes have a sharp tip that scans the surfaces of structures at the level of individual atoms and measures the force of molecular-level interactions. In this case, the team chemically modified the tip to imitate the chemical properties of joint cartilage.
The researchers used the modified tips to probe the surface of normal and lubricin-deficient joints, gaining measurements of the amount of friction between the two surfaces. They also obtained measurements of the roughness and stiffness of the cartilage surface.
When compared with mice that have normal joint cartilage, mice lacking lubricin showed two to three times the amount of friction and their joint surfaces were more than twice as rough. The stiffness of the joint cartilage in mutant mice also was reduced by a factor of five, the researchers found. They noted that these findings are consistent with the significant tissue degeneration in early osteoarthritis.
"It's clear from our findings that lubricin is important for protecting the structural integrity of joints," Coles said.
The researchers next will examine the effects of replacing lubricin on the joint surfaces of mutant mice. They are seeking a better understanding of how lubricin carries out its role as a boundary lubricant, leading perhaps to an improved treatment option for osteoarthritis. Preliminary evidence suggests that lubricin injections may prevent, or at least slow, further deterioration of joint cartilage in the arthritic mice.
Kendall Morgan | EurekAlert!
Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden
The pyrenoid is a carbon-fixing liquid droplet
22.09.2017 | Max-Planck-Institut für Biochemie
Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.
A warming planet
Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.
The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...
Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...
Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!
When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...
For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.
Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...
19.09.2017 | Event News
12.09.2017 | Event News
06.09.2017 | Event News
22.09.2017 | Life Sciences
22.09.2017 | Medical Engineering
22.09.2017 | Physics and Astronomy