Epigenetic regulation by long noncoding RNAs in osteo-/adipogenic differentiation of mesenchymal stromal cells and degenerative bone diseases

Abstract

Bone is a complex tissue that undergoes constant remodeling to maintain homeostasis, which requires coordinated multilineage differentiation and proper proliferation of mesenchymal stromal cells (MSCs). Mounting evidence indicates that a disturbance of bone homeostasis can trigger degenerative bone diseases, including osteoporosis and osteoarthritis. In addition to conventional genetic modifications, epigenetic modifications ( i.e. , DNA methylation, histone modifications, and the expression of noncoding RNAs) are considered to be contributing factors that affect bone homeostasis. Long noncoding RNAs (lncRNAs) were previously regarded as ‘transcriptional noise’ with no biological functions. However, substantial evidence suggests that lncRNAs have roles in the epigenetic regulation of biological processes in MSCs and related diseases. In this review, we summarized the interactions between lncRNAs and epigenetic modifiers associated with osteo-/adipogenic differentiation of MSCs and the pathogenesis of degenerative bone diseases and highlighted promising lncRNA-based diagnostic and therapeutic targets for bone diseases.

Long noncoding RNAs in mesenchymal stromal/stem cells osteogenic differentiation: Implications in osteoarthritis pathogenesis

“…We provided a superficial review of lncRNAs expression and osteoarthritis to clarify what was mentioned and separated the regulation in progenitor and non-progenitor cells, which was not previously published. Again, we really enjoyed the reading by Xia et al [ 1 ] and with this information we hope to further our understanding of lncRNAs and mesenchymal stromal/stem cells regulation.…”

“…We read with great interest the review article by Xia et al [ 1 ], titled “Epigenetic regulation by long noncoding RNAs in osteo-/adipo-genic differentiation of mesenchymal stromal cells and degenerative bone diseases”. We believe the article provides an exceptional description of the effect of epigenetic modifications on gene expression patterns related to skeletal system remodeling.…”

“…In the introduction, MSCs are defined as “a heterogenous population of cells which include fibroblast, myofibroblast and progenitor cells”[ 1 ]. Even though this definition was previously introduced by International Society for Cell & Gene Therapy Mesenchymal Stromal Cell Committee[ 2 ], it can be mis-leading within the present article as authors evaluate the effect of lncRNAs on cells that possess differentiation capacity and not fully differentiated cells (such as fibroblasts).…”

Histone Modifications and Non-Coding RNAs: Mutual Epigenetic Regulation and Role in Pathogenesis

“…LncRNAs are able to interact with protein complexes, referred to as histone writers, erasers and readers of histone modifications, thus recruiting them to certain subnuclear domains and genetic loci [ 44 ]. They serve as a signal for decoding chromatin modifications and act as molecular scaffolds for specific chromatin regulatory complexes that combine and integrate the molecular functions of several histone modifiers, thus adjusting the chromatin structure to a specific target locus [ 45 ]. Being able to sponge miRNAs, lncRNAs are often regulating histone modification via their target miRNAs, forming regulatory axes.…”

The regulatory activities of MALAT1 in the development of bone and cartilage diseases

“…Bone undergoes constant modeling and remodeling to maintain homeostasis, which requires multiple regulations in cell differentiation, proliferation, and apoptosis. Disturbance of bone homeostasis may lead to the pathogenesis and progression of bone diseases, such as osteoporosis (OP), osteoarthritis (OA), and rheumatoid arthritis (RA) ( 7 , 8 ). LncRNAs have been reported to epigenetically regulate the differentiation of mesenchymal stromal cells (MSCs) and the development of diseases ( 9 ).…”