Genome‐wide microRNA screening reveals miR‐582‐5p as a mesenchymal stem cell‐specific microRNA in subchondral bone of the human knee joint

Abstract

Emerging evidence suggests that microRNAs (miRNAs) may be pathologically involved in osteoarthritis (OA). Subchondral bone (SCB) sclerosis is accounted for the knee osteoarthritis (KOA) development and progression. In this study, we aimed to screen the miRNA biomarkers of KOA and investigated whether these miRNAs regulate the differentiation potential of mesenchymal stem cells (MSCs) and thus contributing to SCB. We identified 48 miRNAs in the blood samples in KOA patients (n = 5) through microarray expression profiling detection. After validation with larger sample number, we confirmed hsa‐miR‐582‐5p and hsa‐miR‐424‐5p were associated with the pathology of SCB sclerosis. Target genes prediction and pathway analysis were implemented with online databases, indicating these two candidate miRNAs were closely related to the pathways of pluripotency of stem cells and pathology of OA. Surprisingly, mmu‐miR‐582‐5p (homology of hsa‐miR‐582‐5p) was downregulated in osteogenic differentiation and upregulated in adipogenic differentiation of mesenchymal progenitor C3H10T1/2 cells, whereas mmu‐mir‐322‐5p (homology of hsa‐miR‐424‐5p) showed no change through the in vitro study. Supplementing mmu‐miR‐582‐5p mimics blocked osteogenic and induced adipogenic differentiation of C3H10T1/2 cells, whereas silencing of the endogenous mmu‐miR‐582‐5p enhanced osteogenic and repressed adipogenic differentiation. Further mechanism studies showed that mmu‐miR‐582‐5p was directly targeted to Runx2. Mutation of putative mmu‐miR‐582‐5p binding sites in Runx2 3′ untranslated region (3′UTR) could abolish the response of the 3′UTR‐luciferase construct to mmu‐miR‐582‐5p supplementation. Generally speaking, our data suggest that miR‐582‐5p is an important biomarker of KOA and is able to regulate osteogenic and adipogenic differentiation of MSCs via targeting Runx2. The study also suggests that miR‐582‐5p may play a crucial role in SCB sclerosis of human KOA.

Polysaccharide from angelica sinensis attenuates SNP-Induced Apoptosis in osteoarthritis Chondrocytes by Inducing Autophagy via ERK1/2 Pathway

“…Basal level autophagy plays an important role in cellular homeostasis through the elimination of damaged organelles and aggregated intracellular proteins [16]. On the other hand, during conditions of cellular stress, such as nutrient deprivation/starvation, hypoxia, pathogen infection, radiation or anticancer drug treatment, the level of autophagy is augmented, resulting in adaptation and cell survival (cytoprotective response) [17]. Cartilage degeneration and cell death caused by autophagy inhibition play a crucial role in the process of OA [18].…”

MicroRNA-29b Promotes Subchondral Bone Loss in TMJ Osteoarthritis

“…Recent studies showed that in OA, several miRNAs could regulate the abnormal remodeling of the subchondral bone (Prasadam et al 2016; Liu et al 2019; Wang et al 2019; Zhao et al 2019). The present results revealed that miR-29b plays an important role in the regulation of the BMSC-mediated subchondral bone loss during TMJ-OA, which agreed with the results of previous studies and accordingly showed that miR-29b in BMSCs is multifunctional in different physiologic or pathologic conditions (Kaneto et al 2014; Liu et al 2015; Le et al 2016).…”

Characterization of primary cilia features reveal cell-type specific variability in in vitro models of osteogenic and chondrogenic differentiation

“…C3H10T1/2, MC3T3-E1 and ATDC5 are murine mesenchymal stem cells, preosteoblast and prechondrocyte cell-lines, respectively, that are commonly employed in various in vitro studies, interrogating the mechanisms underlying osteoblast and chondrocyte differentiation, bone disorders and repair (Hino et al, 2018;Lee et al, 2017;Wang et al, 2019;Yao & Wang, 2013). Despite the wide use of these cell-lines, how ciliary features vary in them during native OS and CH differentiation has not been so far investigated.…”