title: Circulating microRNAs as novel biomarkers for bone diseases - Complex signatures for multifactorial diseases?
abstract: Biomarkers are essential tools in clinical research and practice. Useful biomarkers must combine good measurability, validated association with biological processes or outcomes, and should support clinical decision making if used in clinical practice. Several types of validated biomarkers have been reported in the context of bone diseases. However, because these biomarkers face certain limitations there is an interest in the identification of novel biomarkers for bone diseases, specifically in those that are tightly linked to the disease pathology leading to increased fracture-risk. MicroRNAs (miRNAs) are the most abundant RNA species to be found in cell-free blood. Encapsulated within microvesicles or bound to proteins, circulating miRNAs are remarkably stable analytes that can be measured using gold-standard technologies such as quantitative polymerase-chain-reaction (qPCR). Nevertheless, the analysis of circulating miRNAs faces several pre-analytical as well as analytical challenges. From a biological view, there is accumulating evidence that miRNAs play essential roles in the regulation of various biological processes including bone homeostasis. Moreover, specific changes in miRNA transcription levels or miRNA secretory levels have been linked to the development and progression of certain bone diseases. Only recently, results from circulating miRNAs analysis in patients with osteopenia, osteoporosis and fragility fractures have been reported. By comparing these findings to studies on circulating miRNAs in cellular senescence and aging or muscle physiology and sarcopenia, several overlaps were observed. This suggests that signatures observed during osteoporosis might not be specific to the pathophysiology in bone, but rather integrate information from several tissue types. Despite these promising first data, more work remains to be done until circulating miRNAs can serve as established and robust diagnostic tools for bone diseases in clinical research, clinical routine and in personalized medicine.
authors.affiliation: TAmiRNA GmbH, 1190 Vienna, Austria.
authors.forename: Matthias
authors.initials: M
authors.lastname: Hackl
authors.affiliation: Musculoskeletal Quantitative Imaging Research Group, Department of Radiology & Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Ursula
authors.initials: U
authors.lastname: Heilmeier
authors.affiliation: Evercyte GmbH, 1190 Vienna, Austria.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Weilner
authors.affiliation: Evercyte GmbH, 1190 Vienna, Austria; Christian Doppler Laboratory for Biotechnology of Skin Aging, Department of Biotechnology, BOKU - University of Natural Resources and Life Sciences Vienna, 1190 Vienna, Austria. Electronic address: johannes.grillari@boku.ac.at.
authors.forename: Johannes
authors.initials: J
authors.lastname: Grillari
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D001847:Bone Diseases / Q000097:blood*; D000074166:Circulating MicroRNA / Q000097:blood*; D006801:Humans; D008954:Models, Biological; D020412:Multifactorial Inheritance; D010024:Osteoporosis / Q000097:blood / Q000235:genetics
chemical_list: D015415:Biomarkers; D000074166:Circulating MicroRNA
keywords: Aging; Biomarkers; Bone disease; Circulating microRNA; Osteoporosis; Sarcopenia