Osteoarthritis, also known as degenerative arthritis, is a disease that affects joint cartilage, the major weight-bearing "cushion" in joints. The disease results from a combination of wear and tear on cartilage and underlying age-related changes that causes cartilage to deteriorate. Joint trauma can also play a role. Osteoarthritis commonly affects the hands, spine, hips, and knees.
Asahara and other members his laboratory were interested in the question of why some people's joints age normally, while others' spiral toward disease.
The scientists suspected that microRNA could play a role. Once thought of as mere genetic helpers, microRNAs are now known to prevent proteins from being produced by messenger RNA, thus acting as an important layer of regulation for biological processes.
"Recent research findings indicate that non-coding RNA should be involved in our development and in diseases," said Asahara, "but we know little about the role of the non-coding RNA for age-related adult disorders."
Breaking New Ground
The team's interest in one type of microRNA in particular, miR-140, was piqued by other work ongoing in the lab, which was published last year. In this study, the team made the observation that miR-140which is only expressed in cartilagewas reduced in cartilage samples from osteoarthritis patients. This led the team to hypothesize that miR-140 is a regulator in osteoarthritis pathology.
To test this idea, the team tried for several years to make targeted "knockout" mouse models that lacked miR-140. They finally succeeded.
With models lacking miR-140, the scientists were able to figure out its effects. Since the animals lacking miR-140 were short in stature, the scientists concluded that miR-140 affected bone formation during development. The mutant mice were also particularly prone to developing osteoarthritis, suggesti
|Contact: Keith McKeown|
Scripps Research Institute