New York, NY—October 5, 2018
microRNA-based therapeutics may one day help treat bone loss seen in diseases such as osteoporosis and rheumatoid arthritis, according to new research published this week in Nature Communications. The study is the first to identify microRNA-182 as a key regulator of bone health, to provide proof of concept that microRNA-182 inhibitors may be useful to treat certain diseases of the bone, and to show that microRNA-182 may be useful as a biomarker to monitor inflammatory bone diseases.
"Our study is the first exploration of key RNAs that would be used to develop a microRNA-based therapeutic strategy to treat bone diseases," said principal study investigator Baohong Zhao, PhD, assistant scientist in the Arthritis and Tissue Degeneration Program at Hospital for Special Surgery (HSS), and assistant professor at Weill Cornell Medical College, both in New York City. "Inhibition of microRNA-182 could have very promising therapeutic implications in the future disease treatment of inflammatory bone diseases, such as rheumatoid arthritis."
Bone destruction is a major characteristic and severe consequence of multiple skeletal diseases, including osteoporosis and inflammatory arthritis. These diseases have a significant impact on patient quality of life and increase the risk of disability.
MicroRNAs play key roles in a variety of biological and pathological processes and have recently gained increasing clinical attention as promising therapeutic targets or biomarkers. Recent studies support the use of microRNAs for the treatment of cancer, metabolic disorders, and infectious diseases such as hepatitis C virus, but little is known about microRNA’s therapeutic role in bone health.
"Skeletal diseases, such as postmenopausal osteoporosis and inflammatory arthritis, such as rheumatoid arthritis, are very common," said Dr. Zhao. "We set out to identify novel therapeutic targets to treat these refractory diseases. microRNA-182 came out as the top candidate for playing a role in inflammatory bone diseases, in a genome-wide screening of microRNAs."
A genome-wide screening of microRNAs identified microRNA-182 as a regulator of inflammatory osteoclast differentiation. The health of the human skeleton depends on a delicate equilibrium between bone resorption by osteoclasts and bone formation by osteoblasts. Bone destruction in rheumatoid arthritis and postmenopausal osteoporosis is mainly attributable to the abnormal activation of osteoclasts.
In basic science experiments, the researchers demonstrated that deletion of microRNA-182 protects against excessive osteoclastogenesis and bone resorption in models of ovariectomy-induced osteoporosis and inflammatory arthritis. Pharmacological treatment of these diseases with microRNA-182 inhibitors completely suppressed pathologic bone erosion.
In other experiments, the researchers discovered that the level of microRNA-182 expression in humans is strongly correlated with rheumatoid arthritis. "The data reveal a strongly positive correlation of microRNA-182 expression with rheumatoid arthritis pathogenesis and bone resorption," said Dr. Zhao. "In patients with rheumatoid arthritis, we can see much higher levels of this microRNA-182 than in healthy donors."
The researchers also evaluated microRNA-182 levels in 10 patients with rheumatoid arthritis and found anti-inflammation treatment controlled the disease and significantly decreased microRNA-182 levels, returning them to healthy donor levels. "Our promising data indicate that inhibition of microRNA-182 could not only have therapeutic implications," said Dr. Zhao. "microRNA-182 could be also used as a biomarker to track disease progress and potentially the benefits of treatments."
About HSS | Hospital for Special Surgery
HSS is the world’s leading academic medical center focused on musculoskeletal health. At its core is Hospital for Special Surgery, nationally ranked No. 1 in orthopedics (for the ninth consecutive year) and No. 3 in rheumatology by U.S.News & World Report (2018-2019). Founded in 1863, the Hospital has one of the lowest infection rates in the country and was the first in New York State to receive Magnet Recognition for Excellence in Nursing Service from the American Nurses Credentialing Center four consecutive times. The global standard total knee replacement was developed at HSS in 1969. An affiliate of Weill Cornell Medical College, HSS has a main campus in New York City and facilities in New Jersey, Connecticut and in the Long Island and Westchester County regions of New York State. In 2017 HSS provided care to 135,000 patients and performed more than 32,000 surgical procedures. People from all 50 U.S. states and 80 countries travelled to receive care at HSS. In addition to patient care, HSS leads the field in research, innovation and education. The HSS Research Institute comprises 20 laboratories and 300 staff members focused on leading the advancement of musculoskeletal health through prevention of degeneration, tissue repair and tissue regeneration. The HSS Global Innovation Institute was formed in 2016 to realize the potential of new drugs, therapeutics and devices. The culture of innovation is accelerating at HSS as 130 new idea submissions were made to the Global Innovation Institute in 2017 (almost 3x the submissions in 2015). The HSS Education Institute is the world’s leading provider of education on the topic of musculoskeletal health, with its online learning platform offering more than 600 courses to more than 21,000 medical professional members worldwide. Through HSS Global Ventures, the institution is collaborating with medical centers and other organizations to advance the quality and value of musculoskeletal care and to make world-class HSS care more widely accessible nationally and internationally.