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<p>Osteoporosis (OP) is a prevalent bone metabolic disorder. Bone marrow mesenchymal stem cells (BMSCs) serve as key cellular mediators in bone remodeling through their capacity to differentiate into bone-forming osteoblasts, positioning them as promising targets for therapeutic intervention. <i>Morinda officinalis</i> polysaccharide (MOP) is a bioactive compound with medicinal potential. This study aimed to investigate the role and molecular mechanism of MOP in the progression of OP in vitro and in vivo, specifically through promoting osteogenic differentiation of BMSCs. An OP cell model was established by treating BMSCs with 4 µM dexamethasone (DEX). Following DEX induction, cells were treated with various concentrations of MOP. Cell viability was assessed using the Cell Counting Kit-8 assay, while proliferation was assessed through Ki67 immunostaining. Apoptotic and cell cycle distribution were analyzed by flow cytometric. Osteogenic differentiation was examined using Alkaline Phosphatase staining and Alizarin Red S staining. The regulatory relationships among hsa_circ_0001165, insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), and suppressor of cytokine signaling 5 (SOCS5) were validated through RNA Immunoprecipitation, RNA pull-down, and methylated RNA immunoprecipitation quantitative PCR assays. Furthermore, an OP rat model was established by intramuscular injection of 5&#xa0;mg/kg DEX twice weekly for 6 weeks. Rats were subsequently treated with different doses of MOP by gavage for 8 weeks, after which bone mineral density, bone histomorphology, and osteogenic marker expression were evaluated. MOP dose-dependently reversed the DEX-induced suppression of BMSC proliferation, cell cycle progression, and osteogenic differentiation, and also reduced apoptosis. MOP upregulated hsa_circ_0001165 expression; knockdown of hsa_circ_0001165 attenuated these promotive effects of MOP on BMSC proliferation and osteogenic differentiation. Hsa_circ_0001165 directly interacted with the IGF2BP2 protein, thereby enhancing the stability of SOCS5 mRNA. Similarly, knockdown of SOCS5 diminished the enhancing effects of MOP on BMSC proliferation and osteogenic differentiation. Additionally, in vivo results demonstrated that MOP significantly improved bone mineral density (BMD), trabecular bone structure, and osteogenic marker expression in OP rats. MOP alleviates OP by upregulating an hsa_circ_0001165/IGF2BP2 axis, which stabilizes m⁶A-modified SOCS5 mRNA and consequently promotes BMSC osteogenic differentiation.</p>

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Morinda officinalis polysaccharide improves osteoporosis by enhancing m⁶A-modified SOCS5 mRNA stability via regulating the hsa_circ_0001165/IGF2BP2 axis

  • 期刊论文

  • 发表日期：

    2026年3月17日

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  • ZhiBo Zhu,
  • Yi Yang,
  • Yi Liu,
  • LingFeng Liao

摘要

Osteoporosis (OP) is a prevalent bone metabolic disorder. Bone marrow mesenchymal stem cells (BMSCs) serve as key cellular mediators in bone remodeling through their capacity to differentiate into bone-forming osteoblasts, positioning them as promising targets for therapeutic intervention. Morinda officinalis polysaccharide (MOP) is a bioactive compound with medicinal potential. This study aimed to investigate the role and molecular mechanism of MOP in the progression of OP in vitro and in vivo, specifically through promoting osteogenic differentiation of BMSCs. An OP cell model was established by treating BMSCs with 4 µM dexamethasone (DEX). Following DEX induction, cells were treated with various concentrations of MOP. Cell viability was assessed using the Cell Counting Kit-8 assay, while proliferation was assessed through Ki67 immunostaining. Apoptotic and cell cycle distribution were analyzed by flow cytometric. Osteogenic differentiation was examined using Alkaline Phosphatase staining and Alizarin Red S staining. The regulatory relationships among hsa_circ_0001165, insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), and suppressor of cytokine signaling 5 (SOCS5) were validated through RNA Immunoprecipitation, RNA pull-down, and methylated RNA immunoprecipitation quantitative PCR assays. Furthermore, an OP rat model was established by intramuscular injection of 5 mg/kg DEX twice weekly for 6 weeks. Rats were subsequently treated with different doses of MOP by gavage for 8 weeks, after which bone mineral density, bone histomorphology, and osteogenic marker expression were evaluated. MOP dose-dependently reversed the DEX-induced suppression of BMSC proliferation, cell cycle progression, and osteogenic differentiation, and also reduced apoptosis. MOP upregulated hsa_circ_0001165 expression; knockdown of hsa_circ_0001165 attenuated these promotive effects of MOP on BMSC proliferation and osteogenic differentiation. Hsa_circ_0001165 directly interacted with the IGF2BP2 protein, thereby enhancing the stability of SOCS5 mRNA. Similarly, knockdown of SOCS5 diminished the enhancing effects of MOP on BMSC proliferation and osteogenic differentiation. Additionally, in vivo results demonstrated that MOP significantly improved bone mineral density (BMD), trabecular bone structure, and osteogenic marker expression in OP rats. MOP alleviates OP by upregulating an hsa_circ_0001165/IGF2BP2 axis, which stabilizes m⁶A-modified SOCS5 mRNA and consequently promotes BMSC osteogenic differentiation.