Bone is a highly dynamic tissue that is constantly dismantled and rebuilt throughout life by the coordinated and balanced activities of matrix-resorbing osteoclasts, bone-forming osteoblasts and matrix-embedded osteocytes. This system is governed by interconnected signaling pathways, transcription factors, secreted regulators, genetic determinants and epigenetic cues including non-coding RNAs. Canonical Wnt signaling is among the most influential pathways regulating tissue development and homeostasis not limited to but including bone mass under physiological, pathological and therapeutic conditions. Recent evidence demonstrates that many activators and inhibitors of the canonical Wnt signaling pathway are regulated by microRNAs (miRNAs), small non-coding RNAs that are known to control several processes during tissue formation and maintenance, including cell lineage commitment and differentiation. MiRNAs regulate protein abundance by pairing to the 3 untranslated region of coding mRNAs, thereby repressing translation. Physiologically, this system contributes to balance pathway activities in response to signaling molecules. For instance in bone, miRNAs have been shown to participate in the control of osteoblast-mediated bone formation and osteoclast-related bone resorption, thereby contributing to bone mass maintenance. Under pathological conditions, an aberrant miRNA signaling network can promote the onset and progression of a disease such as various types of cancer and osteoporosis. In this context, miRNAs may function as disease-specific biomarkers. More importantly, miRNA delivery or antagonism has been reported to attenuate several diseases under experimental and pre-clinical conditions thereby emerging as novel therapeutic tools. This lecture will provide an update on the function of miRNAs in Wnt signaling in the context of bone health and disease. The important role of miRNAs as novel molecular regulators, diagnostic tools and therapeutic targets in musculoskeletal medicine will be emphasized.
14 May 2016 - 17 May 2016