The role of microRNAs in the peripheral circadian rhythm in cartilage

During ageing, the failure of physiological mechanisms to maintain cartilage homeostasis leads to an increasing risk of the degenerative joint disease, osteoarthritis (OA), a leading cause of disability in the UK. There are no effective disease-modifying drugs to treat OA and with an ageing population, OA is an increasing public health and economic burden with 17 million patients predicted in the UK by 2030.

MicroRNAs, as a class, have been shown to be involved in skeletal development and joint health. Similarly, the peripheral circadian rhythm in cartilage has also been shown to be involved in tissue maintenance. The role of microRNAs in maintaining the circadian rhythm in cartilage has not been addressed. We recently discovered that microRNAs known to have a role in cartilage homeostasis, are regulated in a circadian manner. Moreover, they regulate genes involved in establishing the circadian rhythm. This project aims to explore this in more detail at the molecular level both in cultured cells and in the mouse.
Techniques include: microdissection of joint tissues; histology and imaging; RNA purification and gene expression analyses; subcloning and site-directed mutation; mammalian cell culture; transfection; qRT-PCR; western blot.