Abstract
ABSTRACTThe small non‐coding microRNAs (miRNAs) are post‐transcription regulators that modulate diverse cellular process in bone cells. Because optimal miRNA targeting is essential for their function, single‐nucleotide polymorphisms (SNPs) within or proximal to the loci of miRNA (miR‐SNPs) or mRNA (PolymiRTS) could potentially disrupt the miRNA‐mRNA interaction, leading to changes in bone metabolism and osteoporosis. Recent human studies of skeletal traits using miRNA profiling, genomewide association studies, and functional studies started to decipher the complex miRNA regulatory network. These studies have indicated that miRNAs may be a promising bone marker. This review focuses on human miRNA studies on bone traits and discusses how genetic variants affect bone metabolic pathways. Major ex vivo investigations using human samples supported with animal and in vitro models have shed light on the mechanistic role of miRNAs. Furthermore, studying the miRNAs’ signatures in secondary osteoporosis and osteoporotic medications such as teriparatide (TPTD) and denosumab (DMab) have provided valuable insight into clinical management of the disease. © 2018 The Authors. JBMR Plus Published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research
Highlights
Osteoporosis is characterized by reduced bone strength and deteriorated bone microarchitecture
A study on the differentiation of mesenchymal stem cells (MSCs) showed that Fibroblast growth factor receptor like 1 (FGFRL1) was a modulator of FGFR1/2.(32) Interestingly, a more recent study demonstrated that during osteoblast differentiation, FGFRL1 acted as a positive regulator for FGFR2, but on the flip side, it could promote adipocyte differentiation with FGFR1.(32) This dual-role nature of FGFRL1 supported further the idea of
Glucocorticoid therapy used in treating autoimmune diseases, such as inflammatory bowel disease (IBD) and systemic lupus erythematosus (SLE), could lead to osteoporosis.[120,121] IBD patients are known to have elevated proinflammatory circulating cytokine and increased risk of fracture.[122]. A study investigating the miRNA expressions in peripheral immune cells of ulcerative colitis patients with low bone mineral density (BMD) found that miR-19a was significantly associated with inflammatory marker lL-13.(123) MiR-19a was previously found to be upregulated in postmenopausal osteoporosis.[117] whether miR-19a played a role in inflammation-mediated bone metabolism is still unclear and it requires further study
Summary
Osteoporosis is characterized by reduced bone strength and deteriorated bone microarchitecture. Research in miRNAs and bone biology has grown rapidly over the past years, and studies on the roles of miRNAs in basic cellular functions were reviewed recently.[13,14] Eighty unique miRNAs were identified to associate with BMD, fracture, and osteoporosis in human studies (Supplemental Table S1). MiRNAs were shown to promote osteogenic differentiation of mesenchymal stem cells (MSCs) by suppressing osteogenic inhibitors or by mediating major osteoblastic differentiation and signaling pathways.[17] Human studies on miRNAs over the past 8 years have established links between miRNAs and various skeletal phenotypes including BMD and fracture. Basic fibroblast growth factor (FGF2) is an essential mitogenic growth factor in the FGF polypeptide family It is expressed in the majority of mesenchymal and bone-related cells, including chondrocytes, osteoblasts, adipocytes, and osteolclasts. A study on the differentiation of MSCs showed that FGFRL1 was a modulator of FGFR1/2.(32) Interestingly, a more recent study demonstrated that during osteoblast differentiation, FGFRL1 acted as a positive regulator for FGFR2, but on the flip side, it could promote adipocyte differentiation with FGFR1.(32) This dual-role nature of FGFRL1 supported further the idea of JBMR1 Plus
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