University of Manchester
演題：Understanding circadian rhythms in the musculoskeletal system towards therapies for osteoarthritis and low back pain
Osteoarthritis (OA) is the most prevalent joint disease, causing severe pain, deformity and a loss of mobility. Low back pain (LBP), frequently associated with degeneration of the intervertebral disc (IVD), is the No.1 cause of Years Lived with Disability, with over 80% of the population predicted to experience back pain within their lifetime. Age is a major risk factor for both skeletal conditions. However, the reasons why susceptibility to these conditions increases with age are poorly understood. Consequently, current treatments are limited focusing solely on symptomatic pain relief rather than correcting the underlying pathogenesis and aberrant cell biology. The circadian (24 hourly) clocks in the brain and periphery direct key aspects of physiology through rhythmic control of tissue-specific sets of downstream genes. Symptoms of both conditions are known to show time-of-day effect, suggesting a possible involvement of the clock mechanisms. Work from our group focuses on the roles of circadian clocks in the articular cartilage and IVD. We show that the daily rhythm in these tissues becomes dampened and out-of phase during ageing. Further, our data identify circadian clock disruption in cartilage and IVD as a new target of inflammation. Moreover, we show that mice with targeted knockout of an essential clock gene (BMAL1) in chondrocytes and disc cells have profound, yet tissue-specific degeneration in the articular cartilage and IVD. These findings implicate the local skeletal clock as a key regulatiory mechanism for tissue homeostasis.This new avenue of research holde potential to better understand, and eventually treat these debilitating conditions. In this seminar, I will summarize our key findings on skeletal clocks and their potential implications in health and disease of the joint/spine.
世話人：理学系研究科 深田 吉孝