Morinda officinalis polysaccharide regulates rat bone mesenchymal stem cell osteogenic–adipogenic differentiation in osteoporosis by upregulating miR‐21 and activating the PI3K/AKT pathway

Abstract

Osteoporosis (OP) is a prevailing bone metabolic disease. Morinda officinalis polysaccharide (MOP) has biological activities and medicinal potential. This study explored its mechanism in OP. Rat bone mesenchymal stem cells (rBMSCs) were pretreated with low/high concentrations of MOP and subjected to osteogenic differentiation (OD) or adipogenic differentiation (AD) induction. The protein markers of OD (RUNX2 and BMP2) and AD (CEBPα and PPARγ) and miR-21 expression were detected. miR-21 was overexpressed to study its effects on rBMSC OD and AD. rBMSCs were transfected with miR-21 inhibitor and treated with high concentration of MOP for verification. The targeted relationship between miR-21 and PTEN was verified by bioinformatics and dual-luciferase assay. The PTEN/PI3K/AKT pathway-related proteins were detected. Ovariectomy (OVX)-induced OP rats were treated with MOP. Rat bone mineral density (BMD), serum bone metabolism indexes bone-derived alkaline phosphatase (BALP), and osteocalcin (BGP) levels were assessed by BMD detectors and ELISA kits. miR-21 expression in rBMSCs was detected. After treatment with low/high concentrations of MOP, the OD of rBMSCs was increased and AD was inhibited and miR-21 was upregulated. miR-21 overexpression enhanced the OD of rBMSCs and inhibited AD. miR-21 knockdown reversed the effect of high concentration of MOP on rBMSCs. miR-21 targeted PTEN. After treatment with low/high concentrations of MOP, PI3K, and AKT phosphorylation were increased and the PI3K/AKT pathway was activated. BMD, BALP, BGP, and miR-21 levels in OVX rats were decreased. MOP partially alleviated OP in OVX rats. Briefly, MOP enhanced rBMSC OD and inhibited AD via the miR-21/ PTEN/PI3K/AKT axis.

Molecular mechanism of Achyranthis bidentatae radix and Morindae officinalis radix in osteoporosis therapy: An investigation based on network pharmacology, molecular docking, and molecular dynamics simulations

“…leading to an improvement in bone mineral content, bone mineral density, bone volume fraction, and bone microstructure in Monotropein-treated OVX rats [ [55] , [56] , [57] ]. On the other hand, supplementing MOP to OVX rats can alleviate the progression of OP by inhibiting the peroxisome proliferator-activated receptor-γ coactivator-1α/peroxisome proliferator-activated receptor γ pathway, upregulating miR-21 and activating the PI3K/AKT pathway [ 58 , 59 ]. Researchers obtained MOP crude products from MOR by different extraction methods, which may affect the ability of BMSC-derived exosomes to induce osteoclast differentiation by upregulating miR-101-3p or inhibiting PTGS2 expression [ 12 ].…”

How mesenchymal stem cells transform into adipocytes: Overview of the current understanding of adipogenic differentiation

“…Further study demonstrated that miR-149-3p manipulated alternative lineage choices between adipocytes and osteoblasts by directly targeting FTO, which is involved in adipogenesis mainly by regulating fat accumulation. Additionally, miR-21 overexpression was found to enhance osteogenic differentiation and inhibit adipogenic differentiation via the PI3K/AKT axis in rat BMSCs[ 40 ].…”

Therapeutic approach of natural products that treat osteoporosis by targeting epigenetic modulation

“…Morinda officinalis polysaccharide is a prominent active component found in Morinda officinalis . Studies have shown that it can modulate bone-lipid differentiation of BMSCs in osteoporotic rats via upregulation of miR-21 and activation of the PI3K/AKT axis, indicating its potential as a therapeutic agent for OP ( Wu PY et al, 2022 ). Further research is necessary to fully understand the epigenetic mechanisms underlying the therapeutic effects of Morinda officinalis polysaccharide and other polysaccharides on OP.…”