Abstract
Studies have shown that long non‐coding RNA (lncRNA) MEG3 plays a key role in osteoporosis (OP), but its regulatory mechanism is somewhat incompletely clear. Here, we intend to probe into the mechanism of MEG3 on OP development by modulating microRNA‐214 (miR‐214) and thioredoxin‐interacting protein (TXNIP). Rat models of OP were established. MEG3, miR‐214 and TXNIP mRNA expression in rat femoral tissues were detected, along with TXNIP, OPG and RANKL protein expression. BMD, BV/TV, Tb.N and Tb.Th in tissue samples were measured. Ca, P and ALP contents in rat serum were also determined. Primary osteoblasts were isolated and cultured. Viability, COL‐I, COL‐II and COL‐Χ mRNA expression, PCNA, cyclin D1, OCN, RUNX2 and osteolix protein expresion, ALP content and activity, and mineralized nodule area of rat osteoblasts were further detected. Dual‐luciferase reporter gene and RNA‐pull down assays verified the targeting relationship between MEG3, miR‐214 and TXNIP. MEG3 and TXNIP were up‐regulated while miR‐214 was down‐regulated in femoral tissues of OP rats. MEG3 silencing and miR‐214 overexpression increased BMD, BV/TV, Tb.N, Tb.Th, trabecular bone area, collagen area and OPG expression, and down‐regulated RANKL of femoral tissues in OP rats. MEG3 silencing and miR‐214 overexpression elevated Ca and P and reduced ALP in OP rat serum, elevated osteoblast viability, differentiation ability, COL‐I and COL‐Χ expression and ALP activity, and reduced COL‐II expression of osteoblasts. MEG3 specifically bound to miR‐214 to regulate TXNIP. MEG3 silencing and miR‐214 overexpression promote proliferation and differentiation of osteoblasts in OP by down‐regulating TXNIP, which further improves OP.
Highlights
Long non-coding RNAs (LncRNAs) have been found to regulate innumerable diseases, yet the role of lncRNA maternally expressed gene 3 (MEG3) in osteoporosis (OP) has rarely been discussed
We demonstrated that MEG3 silencing and miR-214 overexpression promote proliferation and differentiation of osteoblasts in OP by downregulating thioredoxininteracting protein (TXNIP), which further improves OP
Long non-coding RNAs (LncRNAs) refer to RNA transcripts (> 200 nucleotides) with no or little proteincoding ability which are capable of modulating gene expression via various mechanisms, such as mRNA splicing and epigenetic silencing [4]
Summary
COL-I, COL-II and COL-Χ contents, ALP content and activity, and mineralized nodule area of rat osteoblasts in each group were further detected. Animals were treated humanely using approved procedures in compliance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The rats were fixed in the prone position to cut the clothing hair on the back. After erythromycin eye ointment was applied to both eyes, the rats were put back into the cages in the prone position. The rats in the sham group were treated in the same way as above except that the uterus was not ligated and the ovaries were not removed
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