Navigation Links
Matrilin-3 gene discovered to prevent onset of osteoarthritis

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 extr acellular 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.


'"/>

Source:Lifespan


Related biology news :

1. Newly-discovered class of genes determines ?and restricts ?stem cell fate
2. Newly discovered virus linked to childhood lung disorders and Kawasaki disease
3. New protein discovered by Hebrew University researchers
4. New RNA polymerase discovered in plants
5. Newly discovered pathway might help in design of cancer drugs
6. New tumor-suppressor gene discovered
7. Newly discovered protein an important tool for sleeping sickness research
8. Function of new cancer genes discovered
9. Evidence of 600-million-year old fungi-algae symbiosis discovered in marine fossils
10. Natural tumor suppressor in body discovered by UCSD medical researchers
11. Enzymes newly discovered role may make it target for arthritis treatment
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:3/6/2017)... Calif. , March 6, 2017 ... and sales technology, today announced Predictive Sales Coach ... for infusing actionable sales intelligence into Salesforce. This ... automatically enable their sales organizations with deep knowledge ... that allow for intelligent engagement. Predictive Sales Coach ...
(Date:3/1/2017)...  Aware, Inc. (NASDAQ: AWRE), a leading supplier of ... Moberg has resigned, effective March 3, 2017, as ... and Treasurer of Aware citing a desire to retire.  ... of the Board of Directors of Aware. ... and co-President, General Counsel has been named Chief Executive ...
(Date:2/26/2017)... 25, 2017  Securus Technologies, a leading provider ... public safety, investigation, corrections and monitoring, announces the ... "Too often, too many offenders return ... jails are trying to tackle this ongoing problem ... and family members. While significant steps are underway, Securus ...
Breaking Biology News(10 mins):
(Date:3/24/2017)... -- Agenus Inc. (NASDAQ: AGEN), an immuno-oncology company with ... today announced participation at the following conferences: ... Maidstone Life Sciences conference "Cancer Immunotherapy Conference" at the ... York, NY . Agenus will participate in three ... Robert B. Stein , M.D., Ph.D., President, R&D ...
(Date:3/23/2017)... ... ... proud to announce it has become the premiere team-building cooking event company in San Diego. ... such as Illumina, HP and Qualcomm, and is ranked #1 in its category on Trip ... its new team building format, a way for teams to not only interact with one ...
(Date:3/23/2017)... 23, 2017  Northwest Biotherapeutics (OTCQB: NWBO) (NW ... therapies for solid tumor cancers, today announced that ... it announced last Friday, March 17, 2017. ... investors securities totaling 28,843,692 shares, comprised of 18,843,692 ... shares of Class C Warrants pre-funded at the ...
(Date:3/23/2017)... LOUISVILLE, Colo. , March 23, 2017  GlobeImmune, ... purchase agreement for the sale of 12,835,490 shares of ... the  NantWorks  ecosystem of companies. In connection with the sale ... GlobeImmune $100,000 in cash and issue to GlobeImmune 200,000 ... common stock. "We are pleased to ...
Breaking Biology Technology: