Morinda Officinalis-derived extracellular vesicle-like particles: Anti-osteoporosis effect by regulating MAPK
Yue Cao1, Xuejun Tan2, Jiawen Shen2
1The Third Clinical Medical College, Guangzhou University of Chinese Medicine, NO.261 and 263, Longxi Avenue, Liwan District, Guangzhou, Guangdong, 510375, People's Republic of China; Department of Medical Technology, Medical College of Shaoguan University, NO. 288, University Road, Zhenjiang District, Shaoguan, Guangdong, 512005, People's Republic of China.
Background:
Postmenopausal osteoporosis (PMOP) is a systemic bone disease characterized by low bone mass and microstructural damage. Morinda Officinalis (MO) contains various components with anti-PMOP activities. Morinda Officinalis-derived extracellular vesicle-like particles (MOEVLPs) are new active components isolated from MO, and no relevant studies have investigated their anti-osteoporosis effect and mechanism.
Purpose:
To investigate the alleviating effect of MOEVLPs on PMOP and the underlying mechanism.
Methods:
Differential centrifugation and ultracentrifugation were used to isolate MOEVLPs from MO. Transmission electron microscopy (TEM), flow nano analyzer, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), agarose gel electrophoresis, and thin-layer chromatography were employed to characterize MOEVLPs. PMOP mouse models were utilized to examine the anti-PMOP effect of MOEVLPs. H&E and immunohistochemical staining were used for drug safety and osteogenic effect assessment. Mouse embryo osteoblast precursor cells (MC3T3-E1) were used in vitro experiments. CCK-8 kit, alizarin red staining, proteomic, bioinformatic analyses, and western blot were used to explore the mechanism of MOEVLPs.
Results:
In this study, MOEVLPs from MO were successfully isolated and characterized. Animal experiments demonstrated that MOEVLPs exhibited specific femur targeting, were non-toxic to the heart, liver, spleen, lung, kidney, and aorta, and possessed anti-PMOP properties. The ability of MOEVLPs to strengthen bone formation was better than that of alendronate. In vitro experiments, results revealed that MOEVLPs did not significantly enhance osteogenic differentiation in MC3T3-E1 cells. Instead, MOEVLPs promoted the proliferation of MC3T3-E1 cells. Proteomic and bioinformatic analyses suggested that the proliferative effect of MOEVLPs was closely associated with the mitogen-activated protein kinase (MAPK) signaling pathway, particularly the altered expression of cAMP response element-binding protein (CREB) and ribosomal S6 kinase 1 (RSK1). Western blot results further confirmed these findings.
Conclusion:
Our studies successfully isolated high-quality MOEVLPs and demonstrated that MOEVLPs can alleviate PMOP by promoting osteoblast proliferation through the MAPK pathway. MOEVLPs have the potential to become a novel and natural anti-PMOP drug.
Insights
Morinda Officinalis-derived extracellular vesicle-like particles (MOEVLPs) show potential as a natural treatment for postmenopausal osteoporosis (PMOP). These particles promote osteoblast proliferation via the MAPK pathway, offering a novel therapeutic approach for bone health.
Area of Science:
- Biotechnology
- Pharmacology
- Cell Biology
Background:
- Postmenopausal osteoporosis (PMOP) is a condition of low bone mass and microstructural damage.
- Morinda Officinalis (MO) contains compounds with anti-PMOP activity.
- Morinda Officinalis-derived extracellular vesicle-like particles (MOEVLPs) are novel active components from MO with uninvestigated anti-osteoporosis effects.
Purpose of the Study:
- To investigate the alleviating effect of MOEVLPs on PMOP.
- To elucidate the underlying mechanism of MOEVLPs in treating PMOP.
Main Methods:
- MOEVLPs were isolated from MO using differential centrifugation and ultracentrifugation.
- Characterization involved TEM, flow nano analyzer, SDS-PAGE, agarose gel electrophoresis, and thin-layer chromatography.
- In vivo (PMOP mouse models) and in vitro (MC3T3-E1 cells) experiments assessed efficacy, safety, and mechanism via H&E, immunohistochemistry, CCK-8, alizarin red staining, proteomics, bioinformatics, and western blot.
Main Results:
- MOEVLPs were successfully isolated and characterized, exhibiting femur targeting and safety.
- MOEVLPs demonstrated anti-PMOP properties in vivo, surpassing alendronate in bone strengthening.
- In vitro, MOEVLPs promoted osteoblast proliferation (MC3T3-E1 cells) via the MAPK pathway, involving CREB and RSK1, rather than osteogenic differentiation.
Conclusions:
- High-quality MOEVLPs were isolated and shown to alleviate PMOP.
- MOEVLPs promote osteoblast proliferation through the MAPK pathway, suggesting a novel mechanism for treating PMOP.
- MOEVLPs hold promise as a natural therapeutic agent for postmenopausal osteoporosis.
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