The emerging role of microRNAs in bone remodeling and its therapeutic implications for osteoporosis

Abstract

Osteoporosis, a common and multifactorial disease, is influenced by genetic factors and environments. However, the pathogenesis of osteoporosis has not been fully elucidated yet. Recently, emerging evidence suggests that epigenetic modifications may be the underlying mechanisms that link genetic and environmental factors with increased risks of osteoporosis and bone fracture. MicroRNA (miRNA), a major category of small noncoding RNA with 20-22 bases in length, is recognized as one important epigenetic modification. It can mediate post-transcriptional regulation of target genes with cell differentiation and apoptosis. In this review, we aimed to profile the role of miRNA in bone remodeling and its therapeutic implications for osteoporosis. A deeper insight into the role of miRNA in bone remodeling and osteoporosis can provide unique opportunities to develop a novel diagnostic and therapeutic approach of osteoporosis.

Keywords: bone fracture; bone remodeling; epigenetics; microRNA; osteoporosis.

Figure 1. Epigenetic modifications underlying the risks of osteoporosis and bone fracture

Osteoporosis is a common and complex disease with multifactorial origin that is influenced by both genes and environments. Epigenetic modifications, especially miRNAs represent a promising area to link genetics and gene expressions with the risks of osteoporosis and bone fracture; ALP, alkaline phosphatase; COL1A1, collagen, type I, α 1; CTR, calcitonin receptor; IBSP, integrin binding sialoprotein; OPN, osteopontin; RANK, the receptor activator of nuclear factor-κ B; TRAP, tartrate-resistant acid phosphatase.

Figure 2. MiRNAs and their roles in osteoblast and osteoclast differentiation

A number of miRNAs have been clearly found and deeply involved in the regulation of osteoblast and osteoclast differentiation, by targeting to bone-related genes and different signaling pathways; ALP, alkaline phosphatase; BMP-7, bone morphogenetic protein-7; BMPR2, bone morphogenetic protein receptor type II; COL1A1, collagen, type I, α 1; CTGF/CCN2, connective tissue growth factor/CCN family 2; DKK1, Dickkopf-1; IBSP, integrin binding sialoprotein; LGR4, leucine-rich repeat-containing G-protein-coupled receptor 4; MMP-13, matrix metalloproteinase-13; OPN, osteopontin; PI3K, phosphatidylinositol 3 kinase; RANKL, the receptor activator of nuclear factor-Κ B ligand; Runx2, runt-related transcription factor 2; STAT3, signal transducer and activator of transcription 3; TGFβ1, transforming growth factor β1.