A gene that is associated with osteoarthritis and skeletal deformities in people has been shown to be responsible for preventing the onset of osteoarthritis in adult mice, according to a recent study led by Rhode Island Hospital. The matrilin-3 gene plays a role in early bone development, controls bone mineral density in adulthood and prevents osteoarthritis later in life.
Mutations in matrilin-3 have previously been linked to certain skeletal disorders and hand osteoarthritis. But this study, reported in the cover article of the August issue of the American Journal of Pathology, is the first to demonstrate that the loss of the gene leads to osteoarthritis, a joint disease that is caused by deterioration of cartilage, and usually occurs later in life.
"Clearly there is a correlation between matrilin-3 and osteoarthritis. Potentially, we could use it as a diagnostic tool or to predict whether someone is likely to develop osteoarthritis," says senior author Qian Chen, PhD, director of cell and molecular biology, and head of orthopaedic biology research at Rhode Island Hospital.
Chen is also a professor of medical science, and holds the Michael G. Ehrlich Chair in Orthopaedic Research, both at Brown Medical School.
The research has also led to an animal model that can be used to study the development of arthritis in real time, Chen says. Previous research has attempted to pinpoint causes of osteoarthritis through other means, such as looking retrospectively at the causes of the disease or inflicting an injury on a joint to mimic a sports injury or trauma.
"In the long term, it helps us understand the mechanism of human osteoarthritis development. Very few molecules have even been associated with osteoarthritis, so this is a huge deal. Now that matrilin-3 has been clearly shown to develop osteoarthritis in an animal model, we can study it further," Chen says.
There are four matrilins, or proteins, that form the extracellular matrix (ECM), which holds cartilage together. Matrilin-1 and -3 are specific to skeleton tissues, while matrilin-2 and -4 are also found in other tissues throughout the body. There has been a link between mutated forms of matrilin-3 and hand osteoarthritis, as well as skeletal disorders such as multiple epiphyseal dysplasia (MED), a disorder that begins in childhood and can include malformation of the hands, feet and knees and abnormal curvature of the spine.
In this study, researchers knocked out matrilin-1 and -3 in mice in order to study their link to osteoarthritis. When matrilin-1 was knocked out, there was no apparent effect. When matrilin-3 was removed, the mice had a normal and fertile lifespan and appeared to have normal skeletal development.
However, without matrilin-3, researchers noticed that during embryonic development, mice developed premature and extended hypertrophy – the phase when cells increase in size to form bone. Later in life, those mice had higher bone mineral density (BMD) and higher rates of osteoarthritis. In people, BMD is a hallmark of certain forms of osteoarthritis.
Compared with mice whose genes had not been altered, the mice lacking matrilin-3 showed significantly higher BMD both in the knee joint and throughout the body at 18 weeks of age, the time when mice typically reach peak bone density. Clinical studies in humans have shown that the prevalence of knee and hip osteoarthritis increases with increasing BMD.
"Our study reveals an unexpected property of matrilin-3 in maintaining proper BMD, a factor that was not previously examined," the authors write. "However, the mechanism of the association between increased bone density and joint degeneration is not known. Our data show that matrilin-3 deficiency results in both the increase of BMD and joint cartilage degeneration, thereby connecting these two events together."
Researchers could not make the connection, however, between a lack of matrilin-3 and skeletal disorders, such as MED. The mice lacking matrilin-3 developed a higher incidence of osteoarthritis in adulthood without developing deformities in childhood.
The results challenge one theory of osteoarthritis – that the disease is caused by degeneration from an abnormal skeletal structure.
"Our study shows that even in those normal looking skeletons, you still develop osteoarthritis. So there's not necessarily a link between those two," Chen says. "Maybe there's something else that causes it, such as stiff bone."
Osteoarthritis affects more than 20 million Americans and is the most common type of arthritis. It is characterized by a breakdown in cartilage, commonly affecting the knees, hips and lower back. While younger people can develop osteoarthritis from joint injuries, the disease most often occurs in people over 65. The causes of osteoarthritis are not known, but they are believed to be both genetic and environmental – such as being overweight or suffering sports injuries.
Meadows beat out shrubs when it comes to storing carbon
23.11.2017 | Norwegian University of Science and Technology
Migrating Cells: Folds in the cell membrane supply material for necessary blebs
23.11.2017 | Westfälische Wilhelms-Universität Münster
Heat from the friction of rocks caused by tidal forces could be the “engine” for the hydrothermal activity on Saturn's moon Enceladus. This presupposes that...
The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.
Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....
The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.
Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...
Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.
That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...
Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.
During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....
15.11.2017 | Event News
15.11.2017 | Event News
30.10.2017 | Event News
23.11.2017 | Information Technology
23.11.2017 | Physics and Astronomy
23.11.2017 | Life Sciences