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.

MicroRNA Regulation of Oxidative Stress‐Induced Cellular Senescence

“…When the participants were subdivided into long-lived and short-lived subgroups, a multiplex of aging biomarker with the expression of miR-211-5p, miR-374a-5p, miR-340-3p, miR-376c-3p, miR-5095, and miR-1225-3p was proposed to be significantly differentially expressed and correlated with lifespan, providing a basis for investigating miRNAs as potential longevity predictors and regulators of aging process [81]. Circulating miRNAs from blood samples have been also investigated as biomarkers of aging-associated diseases, like cardiovascular diseases, neurodegenerative diseases, type 2 diabetes mellitus, and bone diseases [78, 82, 83]. Body fluids other than blood samples are also a reservoir of miRNA biomarkers.…”

miRNA Expression Profile of Saliva in Subjects of Yang Deficiency Constitution and Yin Deficiency Constitution

“…By targeting the mRNAs of protein-coding genes, miRNAs play a critical role in a variety of biological and pathological processes [13][14][15][16]. As a result, using miRNAs as biomarkers have received widespread attention [17][18][19]. While most miRNAs are found intracellularly, a significant number have also been observed extracellularly in saliva, urine and breast milk [20][21][22][23].…”

Identification of suitable reference gene and biomarkers of serum miRNAs for osteoporosis

“…Recently, several groups reported miRNAs circulated in highly stable, cell-free form in body fluids including serum and plasma4567. Because they met the three fundamental criteria of valuable biomarker: measurability, validation and utility, circulating miRNAs had great potential to serve as noninvasive biomarkers for molecular diagnostics89. Only recently, results from circulating miRNAs analysis in patients with osteopenia, osteoporosis and fragility fractures have been reported.…”

“…Meanwhile, Panach et al identified three up-regulated miRNAs (miR-122-5p, miR-125b-5p and miR-21-5p) were valuable biomarkers for osteoporotic fracture14. Due to the diverse nature of study designs, the number and type of regulated miRNAs identified varies significantly9. Specific and sensitive circulating miRNA biomarkers for postmenopausal osteoporosis has not been fully established and their potential of functioning as biomarkers for mechanical unloading induced osteoporosis remain unclear.…”