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Matrilin-3 gene discovered to prevent onset of osteoarthritis

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
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Source:Lifespan


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