METTL3-mediated LINC00657 promotes osteogenic differentiation of mesenchymal stem cells via miR-144-3p/BMPR1B axis. 2022

Jun Peng, and Yulin Zhan, and Yang Zong
Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. drpengjun@hotmail.com.

N6-methyladenosine (m6A) modification plays a crucial role in the progression of osteoporosis (OP). The study aimed to explore the effects of methyltransferase-like 3 (METTL3) in OP. The levels of METTL3, LINC00657, miR-144-3p and BMPR1B were detected using qPCR. Osteogenesis was assessed using alizarin red and alkaline phosphatase (ALP) staining assays. The protein expression of Bglap, Runx2 and Col1a1 was measured by western blot. The targets of LINC00657 and miR-144-3p were screened by bioinformatic analysis. The interaction between miR-144-3p and LINC00657 or BMPR1B was analyzed by dual-luciferase reporter assay and RNA pull-down assay. The results showed that METTL3 was downregulated in OP. METTL3 mediated m6A methylation of LINC00657 to promote the development of osteogenesis. Further study indicated that LINC00657 functioned as a ceRNA to upregulate BMPR1B via sponging miR-144-3p. Additionally, BMPR1B knockdown alleviated the effects of METTL3 on osteogenesis of bone marrow mesenchymal stem cells (BMSCs). Taken together, METTL3 facilitated osteogenic differentiation of BMSCs via the LINC00657/miR-144-3p/BMPR1B axis. Our findings may provide a novel insight of m6A methylation in the development of OP.

UI MeSH Term Description Entries
D008780 Methyltransferases A subclass of enzymes of the transferase class that catalyze the transfer of a methyl group from one compound to another. (Dorland, 28th ed) EC 2.1.1. Methyltransferase
D010012 Osteogenesis The process of bone formation. Histogenesis of bone including ossification. Bone Formation,Ossification, Physiologic,Endochondral Ossification,Ossification,Ossification, Physiological,Osteoclastogenesis,Physiologic Ossification,Endochondral Ossifications,Ossification, Endochondral,Ossifications,Ossifications, Endochondral,Osteoclastogeneses,Physiological Ossification
D010024 Osteoporosis Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis (OSTEOPOROSIS, POSTMENOPAUSAL) and age-related or senile osteoporosis. Age-Related Osteoporosis,Bone Loss, Age-Related,Osteoporosis, Age-Related,Osteoporosis, Post-Traumatic,Osteoporosis, Senile,Senile Osteoporosis,Osteoporosis, Involutional,Age Related Osteoporosis,Age-Related Bone Loss,Age-Related Bone Losses,Age-Related Osteoporoses,Bone Loss, Age Related,Bone Losses, Age-Related,Osteoporoses,Osteoporoses, Age-Related,Osteoporoses, Senile,Osteoporosis, Age Related,Osteoporosis, Post Traumatic,Post-Traumatic Osteoporoses,Post-Traumatic Osteoporosis,Senile Osteoporoses
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D052005 Bone Morphogenetic Protein Receptors, Type I A subtype of bone morphogenetic protein receptors with high affinity for BONE MORPHOGENETIC PROTEINS. They can interact with and undergo PHOSPHORYLATION by BONE MORPHOGENETIC PROTEIN RECEPTORS, TYPE II. They signal primarily through RECEPTOR-REGULATED SMAD PROTEINS. Activin Receptor-Like Kinase 3,Activin Receptor-Like Kinase 6,BMP Type I Receptor,BMP Type IA Receptor,BMP Type IB Receptor,BMPR-I Receptors,BMPR-IA Receptor,BMPR-IB Receptor,Bone Morphogenetic Protein Receptor Type I,Bone Morphogenetic Protein Receptor, Type IA,Bone Morphogenetic Protein Receptor, Type IB,Serine-Threonine Protein Kinase Receptor R6,Type I Bone Morphogenetic Protein Receptors,Type IA Bone Morphogenetic Protein Receptor,Type IB Bone Morphogenetic Protein Receptor,Activin Receptor Like Kinase 3,Activin Receptor Like Kinase 6,BMPR I Receptors,BMPR IA Receptor,BMPR IB Receptor,Serine Threonine Protein Kinase Receptor R6
D059630 Mesenchymal Stem Cells Mesenchymal stem cells, also referred to as multipotent stromal cells or mesenchymal stromal cells are multipotent, non-hematopoietic adult stem cells that are present in multiple tissues, including BONE MARROW; ADIPOSE TISSUE; and WHARTON JELLY. Mesenchymal stem cells can differentiate into mesodermal lineages, such as adipocytic, osteocytic and chondrocytic. Adipose Tissue-Derived Mesenchymal Stem Cell,Adipose Tissue-Derived Mesenchymal Stromal Cell,Adipose-Derived Mesenchymal Stem Cell,Bone Marrow Mesenchymal Stem Cell,Mesenchymal Stromal Cell,Mesenchymal Stromal Cells,Multipotent Bone Marrow Stromal Cell,Multipotent Mesenchymal Stromal Cell,Adipose Tissue-Derived Mesenchymal Stem Cells,Adipose Tissue-Derived Mesenchymal Stromal Cells,Adipose-Derived Mesenchymal Stem Cells,Adipose-Derived Mesenchymal Stromal Cells,Bone Marrow Mesenchymal Stem Cells,Bone Marrow Stromal Cell,Bone Marrow Stromal Cells,Bone Marrow Stromal Cells, Multipotent,Bone Marrow Stromal Stem Cells,Mesenchymal Progenitor Cell,Mesenchymal Progenitor Cells,Mesenchymal Stem Cell,Mesenchymal Stem Cells, Adipose-Derived,Mesenchymal Stromal Cells, Multipotent,Multipotent Bone Marrow Stromal Cells,Multipotent Mesenchymal Stromal Cells,Stem Cells, Mesenchymal,Wharton Jelly Cells,Wharton's Jelly Cells,Adipose Derived Mesenchymal Stem Cell,Adipose Derived Mesenchymal Stem Cells,Adipose Derived Mesenchymal Stromal Cells,Adipose Tissue Derived Mesenchymal Stem Cell,Adipose Tissue Derived Mesenchymal Stem Cells,Adipose Tissue Derived Mesenchymal Stromal Cell,Adipose Tissue Derived Mesenchymal Stromal Cells,Mesenchymal Stem Cells, Adipose Derived,Progenitor Cell, Mesenchymal,Progenitor Cells, Mesenchymal,Stem Cell, Mesenchymal,Stromal Cell, Mesenchymal,Stromal Cells, Mesenchymal,Wharton's Jelly Cell,Whartons Jelly Cells
D035683 MicroRNAs Small double-stranded, non-protein coding RNAs, 21-25 nucleotides in length generated from single-stranded microRNA gene transcripts by the same RIBONUCLEASE III, Dicer, that produces small interfering RNAs (RNA, SMALL INTERFERING). They become part of the RNA-INDUCED SILENCING COMPLEX and repress the translation (TRANSLATION, GENETIC) of target RNA by binding to homologous 3'UTR region as an imperfect match. The small temporal RNAs (stRNAs), let-7 and lin-4, from C. elegans, are the first 2 miRNAs discovered, and are from a class of miRNAs involved in developmental timing. RNA, Small Temporal,Small Temporal RNA,miRNA,stRNA,Micro RNA,MicroRNA,Primary MicroRNA,Primary miRNA,miRNAs,pre-miRNA,pri-miRNA,MicroRNA, Primary,RNA, Micro,Temporal RNA, Small,miRNA, Primary,pre miRNA,pri miRNA

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