MicroRNA-21 controls the development of osteoarthritis by targeting GDF-5 in chondrocytes

Osteoarthritis is a common cause of functional deterioration in older adults and is an immense burden on the aging population. Altered chondrogenesis is the most important pathophysiological process involved in the development of osteoarthritis. However, the molecular mechanism underlying the regulation of chondrogenesis in patients with osteoarthritis requires further elucidation, particularly with respect to the role of microRNAs. MiR-21 expression in cartilage specimens was examined in 10 patients with knee osteoarthritis and 10 traumatic amputees. The effect of miR-21 on chondrogenesis was also investigated in a chondrocyte cell line. The effect of miR-21 on the expression of growth differentiation factor 5 (GDF-5) was further assessed by luciferase reporter assay and western blot. We found that endogenous miR-21 is upregulated in osteoarthritis patients, and overexpression of miR-21 could attenuate the process of chondrogenesis. Furthermore, we identified GDF-5 as the direct target of miR-21 during the regulation of chondrogenesis. Our data suggest that miR-21 has an important role in the pathogenesis of osteoarthritis and is a potential therapeutic target. A small regulatory RNA molecule called microRNA-21 seems to be over-expressed in the joints of people with osteoarthritis, leading to reduced rates of cartilage formation. Yukun Zhang, Shuhua Yang and their colleagues at the Huazhong University of Science and Technology, China, measured levels of microRNA-21 in cartilage tissue from 10 people with osteoarthritis. As controls, they measured the same levels in 10 other people with traumatic amputation. The researchers found elevated expression levels of microRNA-21 in the osteoarthritis patients. In a laboratory experiment, the researchers showed that microRNA-21 exposure inhibited the growth and maturation of cartilage cells by repressing the activity of a protein called growth differentiation factor 5 (GDF-5), which is involved in cartilage remodeling. The findings suggest that microRNA-21 and GDF-5 could be good candidate drug targets to treat osteoarthritis.