LncRNA XIXT promotes osteogenic differentiation of bone mesenchymal stem cells and alleviates osteoporosis progression by targeting miRNA-30a-5p. 2019

H-L Zhang, and X-Y Du, and Q-R Dong
Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou, China. qirong_dong@163.com.

OBJECTIVE To uncover the role of XIXT in influencing the osteogenesis of hBMSCs by adsorbing microRNA-30a-5p (miRNA-30a-5p) to upregulate RUNX2. METHODS The serum samples were collected from osteoporosis patients and normal people. hBMSCs were isolated from femoral head tissues. The serum levels of XIXT and miRNA-30a-5p were determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The expression levels and activities of the osteogenic differentiation-related genes in hBMSCs after transfection of sh-XIXT, sh-RUNX2, miRNA-30a-5p mimic, and inhibitor were detected by qRT-PCR, Western blot, ALP activity assay, and alizarin red staining. The Dual-Luciferase Reporter Gene Assay was performed to confirm the binding of XIXT to miRNA-30a-5p, as well as the binding of miRNA-30a-5p to RUNX2. RESULTS LncRNA XIXT was significantly downregulated, and miRNA-30a-5p was upregulated in the serum of osteoporosis patients. The osteogenic differentiation-related genes (ALP, RUNX2) and XIXT were markedly upregulated in a time-dependent manner, while miRNA-30a-5p level gradually decreased in hBMSCs with the prolongation of osteogenesis. The knockdown of XIXT inhibited the osteogenic differentiation of hBMSCs. In hBMSCs, XIXT regulated RUNX2 expression by targeting miRNA-30a-5p. The knockdown of miRNA-30a-5p partially reversed the inhibitory effect of XIXT on the osteogenesis of hBMSCs. However, the downregulated RUNX2 reversed the promotive effect of miRNA-30a-5p on the osteogenesis of hBMSCs. CONCLUSIONS LncRNA XIXT upregulated RUNX2 by absorbing miRNA-30a-5p, and thus induced hBMSCs osteogenesis to alleviate osteoporosis.

UI MeSH Term Description Entries
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
D001854 Bone Marrow Cells Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells. Bone Marrow Cell,Cell, Bone Marrow,Cells, Bone Marrow,Marrow Cell, Bone,Marrow Cells, Bone
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
D000070416 Antagomirs Chemically-engineered oligonucleotides used to selectively inhibit expression of target genes through sequence-specific binding of corresponding microRNA (miRNA) sites. Antagomir,Anti-miR,Anti-miRs,Blockmirs,Anti miR,Anti miRs
D001483 Base Sequence The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence. DNA Sequence,Nucleotide Sequence,RNA Sequence,DNA Sequences,Base Sequences,Nucleotide Sequences,RNA Sequences,Sequence, Base,Sequence, DNA,Sequence, Nucleotide,Sequence, RNA,Sequences, Base,Sequences, DNA,Sequences, Nucleotide,Sequences, RNA
D016415 Sequence Alignment The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms. Sequence Homology Determination,Determination, Sequence Homology,Alignment, Sequence,Alignments, Sequence,Determinations, Sequence Homology,Sequence Alignments,Sequence Homology Determinations
D050659 Core Binding Factor Alpha 1 Subunit A transcription factor that dimerizes with CORE BINDING FACTOR BETA SUBUNIT to form core binding factor. It contains a highly conserved DNA-binding domain known as the runt domain and is involved in genetic regulation of skeletal development and CELL DIFFERENTIATION. AML3 Transcription Factor,Acute Myeloid Leukemia 3 Protein,CBFA-1 Protein,CBFA1 Protein,CBFalpha Runt Domain Transcription Factor 1,CBFalpha1 Protein,Osf2 Transcription Factor,PEBP2alphaA Protein,Runx2 Protein,SEF1 Protein,SL3-3 Enhancer Factor 1,CBFA 1 Protein,SL3 3 Enhancer Factor 1

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