miR‑98‑5p promotes osteoblast differentiation in MC3T3‑E1 cells by targeting CKIP‑1

Abstract

Casein kinase 2-interacting protein 1 (CKIP-1) is a negative regulator for bone formation. Previously, using bioinformatics analysis, CKIP‑1 has been predicted to serve the role of target gene of miR‑98‑5p. In the present study, the potential role of miR‑98‑5p in regulating osteoblast differentiation through CKIP‑1 was investigated. Following pre‑treatment with microRNA (miR)‑98‑5p agomir or miR‑98‑5p antagomir, MC3T3‑E1 cells were cultured in an osteoinductive medium. Subsequently, the expression of miR‑98‑5p, CKIP‑1 and levels of osteoblast differentiation markers, including alkaline phosphatase, matrix mineralization, osteocaicin, collagen type I, runt‑related transcription factor 2 and osteopontin were assayed. Using a dual‑luciferase reporter assay, it was demonstrated that CKIP‑1 was the target gene of miR‑98‑5p. miR‑98‑5p was upregulated as a result of treatment with miR‑98‑5p agomir and promoted osteoblast differentiation. Conversely, miR‑98‑5p antagomir inhibited miR‑98‑5p expression and osteoblast differentiation. miR‑98‑5p targeted CKIP‑1 by binding to its 3'‑untranslated region. Furthermore, miR‑98‑5p overexpression decreased the protein levels of CKIP‑1 and inhibition of miR‑98‑5p increased the protein levels of CKIP‑1. The results of the present study indicated that CKIP‑1 was a target gene of miR‑98‑5p and that miR‑98‑5p regulated osteoblast differentiation in MC3T3‑E1 cells by targeting CKIP‑1.

The effect of QiangGuYin on osteoporosis through the AKT/mTOR/autophagy signaling pathway mediated by CKIP-1

“…Xi et al reported that the AKT/mTOR signaling pathway participates in the inhibition of osteoporosis by promoting osteoblast proliferation, differentiation and bone formation in vitro and in vivo models [29]. In this study, we found that overexpression of CKIP-1 significantly inhibits the AKT/mTOR pathway, while OGY treatment reactivates the inhibited AKT/mTOR pathway, which is consistent with previous studies [9,[30][31][32][33][34][35]. Therefore, CKIP-1 acts as an intermediary between QGY and AKT/mTOR signaling crosstalk.…”

Identification of biomarkers and regulatory networks for cartilage damage patients

“…In this study, WNT5A was significantly up-regulated with log2 fold change 1.60 and p value 4.47 × 10 −4 , which was in accordance with the results that when the cartilage was damaged, miR-92a-3p repressed the chondrogenic differentiation and reduced cartilage matrix synthesis by enhancing the expression of WNT5A [41]. MiR-98-5p is involved in the regulation of osteoblast differenti- ation and promotes its differentiation through targeting and regulating CKIP-1 expression [42].…”

Roles of MicroRNAs in Bone Destruction of Rheumatoid Arthritis

“…MiR-1-3p (Zhou et al, 2020) directly targeted and inhibited the expression of hypoxia-inducible factor 1-alpha inhibitor (HIF1AN), miR-5100 (Wang et al, 2017) directly inhibited the expression of Tob2, miR-7-5p (Chen B. et al, 2018) directly targeted chemokine-like receptor 1 (CMKLR1), miR-590-3p (Wu S. et al, 2016) directly inhibited the expression of adenomatous polyposis coli (APC), and miR-98 promoted osteogenic differentiation via targeting HMGA2 in human BMSCs (Gao et al, 2018). Liu et al (2018) Interestingly, in one study, miR-98-5p negatively regulated the expression of casein kinase 2 interacting protein-1 (CKIP-1) gene and protein to promote the osteogenic differentiation of MC3T3-E1 cells (Liu et al, 2018). But another study in three types of cells (MC3T3-E1 cells, mouse and human BMSCs), miR-98-5p inhibited osteogenic differentiation by targeting HMGA2 (Zheng et al, 2019).…”