MicroRNA Functions in Osteogenesis and Dysfunctions in Osteoporosis

Abstract

MicroRNAs (miRNAs) are critical post-transcriptional regulators of gene expression that control osteoblast mediated bone formation and osteoclast-related bone remodelling. Deregulation of miRNA mediated mechanisms is emerging as an important pathological factor in bone degeneration (e.g., osteoporosis) and other bone-related diseases. MiRNAs are intriguing regulatory molecules that are networked with cell signaling pathways and intricate transcriptional programs through ingenuous circuits with remarkably simple logic. This overview examines key principles by which miRNAs control differentiation of osteoblasts as they evolve from mesenchymal stromal cells during osteogenesis, or of osteoclasts as they originate from monocytic precursors in the hematopoietic lineage during osteoclastogenesis. Of particular note are miRNAs that are temporally up-regulated during osteoblastogenesis (e.g., miR-218) or osteoclastogenesis (e.g., miR-148a). Each miRNA stimulates differentiation by suppressing inhibitory signalling pathways (‘double-negative’ regulation). The excitement surrounding miRNAs in bone biology stems from the prominent effects that individual miRNAs can have on biological transitions during differentiation of skeletal cells and correlations of miRNA dysfunction with bone diseases. MiRNAs have significant clinical potential which is reflected by their versatility as disease-specific biomarkers and their promise as therapeutic agents to ameliorate or reverse bone tissue degeneration.

MicroRNAs as novel regulators of stem cell fate

“…Increasing evidences suggests that miRNAs are an integral part of regulating bone and cartilage formation, metabolism, homeostasis, osteogenesis, and chondrogensis [115,116] . Osteoblast differentiation from bone marrow stromal cells undergoes three stages: pre-osteoblast (proliferation), osteoblast/pre-osteocyte (matrix maturation), and osteocyte (mineralization) [117] .…”

Regulatory Loops Consisting of Transcription Factors and microRNA Species Determine the Mineralizing Characteristics of Cell Phenotypes — Implications for Bone Engineering and Prevention of Soft Tissue Mineralization

“…However, this is a simplification of the issue, since the acquired osteoblastic or mineralizing phenotype is secured by a balanced impact of microRNAs targeting osteogenic markers (or modulators) like BMP-2, SMADs, Runx2, Osterix (SP7), Dkk-1, and RANKL and others, a loss of calcification inhibitors like MGP and Fetuin-A, and finally a loss of smooth muscle cell markers like α-actin and certain MHC-class of antigens, as shown by Goettsch and co-workers [18]. This major compilation of published literature indicates that several microRNAs well known to be down-regulated in osteoblasts (like the miR-species 23a, 24, 27a, 29a, 34c, 133a, 135a, 149, 204, and 328) [36][37][38][39] are not necessarily down-regulated in "mineralizing" or "calcifying" vascular cells.…”

Osteosarkoma pediatrikoarekiko suszeptibilitatean inplikatuta dauden aldaera genetikoak

“…Hala ere, miRNAek osteosarkomagenesian duten papera oraindik ez da guztiz ezagutzen. Seiehun miRNA baino gehiagok parte hartzen dute osteogenesiaren erregulazioan; hori dela eta, miRNA horien edozein adierazpen-aldaketak hezur-gaixotasunak eragin ditzakeela uste da [50]. Esate ba-…”