Emerging roles for long noncoding RNAs in skeletal biology and disease

Abstract

Normal skeletal development requires tight coordination of transcriptional networks, signaling pathways, and biomechanical cues, and many of these pathways are dysregulated in pathological conditions affecting cartilage and bone. Recently, a significant role has been identified for long noncoding RNAs (IncRNAs) in developing and maintaining cellular phenotypes, and improvements in sequencing technologies have led to the identification of thousands of IncRNAs across diverse cell types, including the cells within cartilage and bone. It is clear that IncRNAs play critical roles in regulating gene expression. For example, they can function as epigenetic regulators in the nucleus via chromatin modulation to control gene transcription, or in the cytoplasm, where they can function as scaffolds for protein-binding partners or modulate the activity of other coding and noncoding RNAs. In this review, we discuss the growing list of IncRNAs involved in normal development and/or homeostasis of the skeletal system, the potential mechanisms by which these IncRNAs might function, and recent improvements in the methodologies available to study IncRNA functions in vitro and in vivo. Finally, we address the likely utility of IncRNAs as biomarkers and therapeutic targets for diseases of the skeletal system, including osteoarthritis, osteoporosis, and in cancers of the skeletal system.

LncRNA LINC00311 Promotes the Proliferation and Differentiation of Osteoclasts in Osteoporotic Rats Through the Notch Signaling Pathway by Targeting DLL3

“…The findings of a recent study regarding dosage compensation, imprinting, and homeotic gene expression revealed that individual large intervening noncoding RNAs (lincRNAs) could function as the interface between specific chromatin remodeling activities and DNA, suggesting they are pervasively transcribed in the genome [22]. LncRNAs have been employed as biomarkers and therapeutic targets in various skeletal diseases including osteoarthritis and osteoporosis, as well as in cancers related to the skeletal system [23], among which the lncRNA DANCR has been observed to act as a regulatory element in patients suffering from osteoporosis [9]. Elevated expression of the lncRNA MyoD has been detected in skeletal muscle cells, and elevated lncRNA HOTAIR expression has been observed in osteosarcoma tissues [24,25].…”

High‐depth transcriptomic profiling reveals the temporal gene signature of human mesenchymal stem cells during chondrogenesis

“…Initially referred to as genomic remnants, lncRNAs are gaining remarkable attention as crucial molecules in cellular maintenance and lineage commitment (69,70). Recently, a growing number of lncRNAs have been identified as important players in musculoskeletal development and diseases (71). In this study, we identified 230 modular lncRNA candidates.…”

lncRNAs: function and mechanism in cartilage development, degeneration, and regeneration

“…In the process of detecting the expression of lncRNAs between different tissues or species, RNA-seq retains the gold standard to identify novel lncRNAs. Second, structure, subcellular location, and binding partner are the three main approaches to predict the function of lncRNAs [33]. LncRNAs do not have the same sequence conservation as protein-coding genes [128].…”

“…Cartilage could be divided into three types: hyaline, elastic, and fibrocartilage [33]. Cartilage was thought of as a simple structure, because it contains only one type of cell and its extracellular matrix (ECM) contains only three components: water, collagen, and proteoglycan [34].…”