MicroRNA miR-18a-3p promotes osteoporosis and possibly contributes to spinal fracture by inhibiting the glutamate AMPA receptor subunit 1 gene (GRIA1)

Abstract

The promoting role that miR-18a-3p plays in osteoporosis (OP) has been previously described. However, the detailed mechanisms remain unclear. Bone tissues were collected from healthy patients, OP patients, and patients with osteoporotic spinal fractures. An osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) was constructed to detect the expression of miR-18a-3p and glutamate AMPA receptor subunit 1 (GRIA1). Alkaline phosphatase (ALP) activity and a qRT-PCR analysis were used to detect ALP content, alizarin red S staining was used to detect calcium deposition, and qRT-PCR was used to evaluate runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), and osteopontin (OPN) expression levels. A dual-luciferase reporter and RNA pull-down assay was used to verify the targeted correlation between miR-18a-3p and GRIA1. We observed an increase in miR-18a-3p expression and a decrease in GRIA1 expression in OP and osteoporotic vertebral fracture patients. Upregulation of miR-18a-3p restrained the activity and expression of ALP in hBMSCs, inhibited the expression of RUNX2, OCN, and OPN, and inhibited calcium deposition. Knockdown of miR-18a-3p or upregulation of GRIA1 promoted osteogenic differentiation. Our findings indicate that miR-18a-3p promotes OP progression by regulating GRIA1 expression, suggesting that targeting miR-18a-3p/GRIA1 may be a therapeutic strategy for OP.

Investigating the Differential Circulating microRNA Expression in Adolescent Females with Severe Idiopathic Scoliosis: A Proof-of-Concept Observational Clinical Study

“…Bioinformatic analysis revealed the differentially expressed miRNAs targeted genes involved in cell signaling pathways that regulated bone homeostasis and also suggested an association with several diseases, including scoliosis, spinal curvature, and other bone characteristics. Furthermore, some miRNAs had already been described for their role in other orthopedic pathologies[ 51 , 52 , 74 , 75 , 76 ]. Three miRNAs were down-regulated in our AIS patients: miR-1294, miR-200a, and miR-548m.…”

The miR-19a/Cylindromatosis Axis Regulates Pituitary Adenoma Bone Invasion by Promoting Osteoclast Differentiation

“…For example, in lung cancer, miR-17 promotes osteoclast differentiation by targeting PTEN and mediates tumor bone metastasis [22]. miR-20a inhibits hypoxia-induced osteoclast differentiation by regulating the expression of autophagy-related proteins [29], and miR-18a-3p promotes osteoporosis and fracture by inhibiting the glutamate AMPA receptor subunit 1 gene [30]. miR-19, as a subfamily of the miR-17/92 cluster, plays essential roles in many diseases, potentiating NF-кB activity in inflammation and promoting the malignancy of osteosarcoma as well as regulating bone metabolism, which have been reported in several studies.…”