BMSC-derived exosomal miR-27a-3p and miR-196b-5p regulate bone remodeling in ovariectomized rats

Abstract

Background In the bone marrow microenvironment of postmenopausal osteoporosis (PMOP), bone marrow mesenchymal stem cell (BMSC)-derived exosomal miRNAs play an important role in bone formation and bone resorption, although the pathogenesis has yet to be clarified. Methods BMSC-derived exosomes from ovariectomized rats (OVX-Exo) and sham-operated rats (Sham-Exo) were co-cultured with bone marrow-derived macrophages to study their effects on osteoclast differentiation. Next-generation sequencing was utilized to identify the differentially expressed miRNAs (DE-miRNAs) between OVX-Exo and Sham-Exo, while target genes were analyzed using bioinformatics. The regulatory effects of miR-27a-3p and miR-196b-5p on osteogenic differentiation of BMSCs and osteoclast differentiation were verified by gain-of-function and loss-of-function analyses. Results Osteoclast differentiation was significantly enhanced in the OVX-Exo treatment group compared to the Sham-Exo group. Twenty DE-miRNAs were identified between OVX-Exo and Sham-Exo, among which miR-27a-3p and miR-196b-5p promoted the expressions of osteogenic differentiation markers in BMSCs. In contrast, knockdown of miR-27a-3p and miR-196b-5p increased the expressions of osteoclastic markers in osteoclast. These 20 DE-miRNAs were found to target 11435 mRNAs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that these target genes were involved in several biological processes and osteoporosis-related signaling pathways. Conclusion BMSC-derived exosomal miR-27a-3p and miR-196b-5p may play a positive regulatory role in bone remodeling.

Human umbilical cord mesenchymal stem cells derived extracellular vesicles alleviate salpingitis by promoting M1–to–M2 transformation

“…The use of hucMSC-EV has shown beneficial effects in a variety of diseases, such as lung disease ( Willis et al, 2020 ; Willis et al, 2021 ), oxygen-Induced multi-organ disease ( Fernandez-Gonzalez et al, 2021 ), preeclamptic lung Injury ( Taglauer et al, 2022 ), various detrimental sequalae of hyperoxia exposure ( Reis et al, 2021 ), cornea disease ( McKay et al, 2021 ), hepatic fibrosis ( Rong et al, 2019 ), etc. In rat calvarial defects, miR-196a ( Qin et al, 2016 ), miR-27a, and miR-206 ( Lai et al, 2022 ) positively regulate the expression of osteogenic genes and osteoblast differentiation to stimulate bone formation ( Liu et al, 2018 ). In a mouse model of Alzheimer’s disease, miR-21 and miR-181c effectively reduced amyloid-β accumulation and increased synaptic protein expression and miR-21 levels in the brains of APP/PS1 mice ( Cui et al, 2018 ).…”

miR‐196b‐5p Regulates Osteoblast and Osteoclast Differentiation and Bone Homeostasis by Targeting SEMA3A

“…Of note, the anti‐osteogenic role of miR‐196b‐5p we observed contradicts a recently published article that reported an in vitro pro‐osteogenic effect of miR‐196b‐5p on rat BMSCs without investigating the underlying mechanism. ( 32 ) Although the exact reason remains unknown, the discrepancy may result from the different cellular context of different BMSCs between mouse and rat.…”

A potential function for MicroRNA-124 in normal and pathological bone conditions

“…The formed axes either positively or negatively regulate many bone conditions. Lai et al showed that miR-27a-3p and miR-196b-5p help BMSCs differentiate into osteoblasts [ 68 ]. The miR-608/SP7 axis and circRNA hsa_circ_0001421/miR-608 partially control human adipose mesenchymal stem cell (hAMSC) osteoblastic differentiation, suggesting that hAMSCs can be used to treat osteoporosis [ 69 ].…”