Exosomes as a Novel Approach to Reverse Osteoporosis: A Review of the Literature

Xie, Xudong; Xiong, Yuan; Hu, Liangcong; Zhou, Wu; Xue, Hang; Lin, Ze; Chen, Lang; Yan, Chenchen; Mi, Bobin; Liu, Guohui

doi:10.3389/fbioe.2020.594247

Cited by 21 publications

(27 citation statements)

References 85 publications

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“…Osteoporosis (OP) is a multifactorial skeletal disease with an increased risk of fracture [ 1 ]. With the extension of mean life expectancy and aging, the prevalence of OP is progressively raising [ 2 ]. The prevalence rates of people over 50 and 60 years old were 19.2% and 32% in China according to an epidemiologic survey in 2018 [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Exploring Quercetin Anti-Osteoporosis Pharmacological Mechanisms with In Silico and In Vivo Models

Yuan

Cai

et al. 2022

Life

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Since osteoporosis critically influences the lives of patients with a high incidence, effective therapeutic treatments are important. Quercetin has been well recognized as a bone-sparing agent and thus the underlying mechanisms warrant further investigation. In the current study, the network pharmacology strategy and zebrafish model were utilized to explain the potential pharmacological effects of quercetin on osteoporosis. The potential targets and related signaling pathways were explored through overlapping target prediction, protein–protein interaction network construction, and functional enrichment analysis. Furthermore, we performed docking studies to verify the specific interactions between quercetin and crucial targets. Consequently, 55 targets were related to osteoporosis disease among the 159 targets of quercetin obtained by three database sources. Thirty hub targets were filtered through the cytoNCA plugin. Additionally, the Gene Ontology functions in the top 10 respective biological processes, molecular functions, and cell components as well as the top 20 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were depicted. The most significance difference in the KEGG pathways was the TNF signaling pathway, consisting of the Nuclear Factor Kappa B Subunit (NF-κB), Extracellular Regulated Protein Kinases (ERK) 1/2, Activator Protein 1 (AP-1), Interleukin 6 (IL6), Transcription factor AP-1 (Jun), and Phosphatidylinositol 3 Kinase (PI3K), which were probably involved in the pharmacological effects. Moreover, molecular docking studies revealed that the top three entries were Interleukin 1 Beta (IL1B), the Nuclear Factor NF-Kappa-B p65 Subunit (RelA), and the Nuclear Factor Kappa B Subunit 1 (NFKB1), respectively. Finally, these results were verified by alizarin red-stained mineralized bone in zebrafish and related qPCR experiments. The findings probably facilitate the mechanism elucidation related to quercetin anti-osteoporosis action.

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Section: Introductionmentioning

confidence: 99%

Exploring Quercetin Anti-Osteoporosis Pharmacological Mechanisms with In Silico and In Vivo Models

Yuan

Cai

et al. 2022

Life

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“…As Exo can be safely applied and possesses potent osteogenic abilities, using Exo to reverse OP is promising (Xie X et al. 2020 ). Different studies have shown a relationship between the application of Exo and osteogenic differentiation of MSCs or a relationship with the activity of osteoblasts.…”

Section: Discussionmentioning

confidence: 99%

“…Exosomal miRNAs are increasingly thought to be major regulators of gene expression and control the differentiation and activities of osteoclasts (Xie X et al. 2020 ; Hensley and McAlinden 2021 ). With the aid of bioinformatics prediction and microarray analyses, the PTGS2 gene was identified and found to be downregulated, and miR-101-3p was upregulated in both MOP-treated rats and MOP-Exo.…”

Section: Discussionmentioning

confidence: 99%

Morinda officinalis polysaccharide enable suppression of osteoclastic differentiation by exosomes derived from rat mesenchymal stem cells

Wu¹,

Feng²,

Huang³

et al. 2022

Pharmaceutical Biology

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Context Morinda officinalis F.C. How. (MO) (Rubiaceae) can strengthen bone function. Objective To examine the functional mechanism and effect of MO polysaccharides (MOPs) in rats with glucocorticoid-induced osteoporosis (GIOP). Materials and methods Rats with GIOP were treated with 5, 15 or 45 mL/kg of MOP [ n = 15 for each dose, intraperitoneal (i.p.) injection every other day for 8 weeks]. The body weight of rats and histomorphology of bone tissues were examined. Bone marrow mesenchymal stem cells (BMSCs)-derived exosomes (Exo) were collected and identified. Bone marrow-derived macrophages (BMMs) were induced to differentiate into osteoclasts and treated with BMSC-Exo for in vitro studies. Results MOP reduced the body weight (5, 15, or 45 mg/kg MOP vs. phosphate-buffered saline: 8%, 15% and 25%, p < 0.01), elevated the bone volume to tissue volume (BV/TV), mean trabecular thickness (Tb.Th), mean trabecular number (Tb.N) and mean connectivity density (Conn.D) (40–86%, p < 0.01), decreased the mean trabecular separation/spacing (Tb.Sp) (22–37%, p < 0.01), increased the cortical bone continuity (35–90%, p < 0.01) and elevated RUNX family transcription factor 2 and RANK levels (5–12%, p < 0.01), but suppressed matrix metallopeptidase 9 and cathepsin K levels (9–20%, p < 0.01) in femur tissues. BMSC-Exo from MOP-treated rats (MOP-Exo) suppressed osteoclastic differentiation and proliferation of BMMs. The downregulation of microRNA-101-3p (miR-101-3p) or the upregulation of prostaglandin-endoperoxide synthase 2 (PTGS2) blocked the functions of MOP-Exo. Discussion and conclusions MOP inhibits osteoclastic differentiation and could potentially be used for osteoporosis management. This suppression may be enhanced by the upregulation of miR-101-3p or the inhibition of PTGS2.

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“…The composition of EVs has a crucial influence on their biological functions; as transmitters, EVs can activate cell surface receptor binding on target cells through proteins and bioactive lipid ligands, thereby inducing intracellular signaling and regulating the biological activity of the target cells. Besides, EVs can deliver their contents to target cells by fusing with the plasma membrane [ 17 , 32 ]. Figure 1 shows the biogenesis and secretion of EVs and their effects on target cells.…”

Section: The Characteristics Of Extracellular Vesiclesmentioning

confidence: 99%

“…The circulating EVs can maintain systemic immune homeostasis and regulate psychological stress-induced sterile inflammation by transmitting immunomodulatory signals [ 10 ]. Similarly, EVs can regulate the function of osteoblasts and osteoclasts, and consequently have a potential impact on osteoporosis [ 17 ]. Therefore, this review aims to evaluate whether EVs act as mediators of psychosocial stress and osteoporosis.…”

Section: Introductionmentioning

confidence: 99%

Extracellular Vesicles: Potential Mediators of Psychosocial Stress Contribution to Osteoporosis?

Wuertz‐Kozak

Kuehl

et al. 2021

IJMS

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Osteoporosis is characterized by low bone mass and damage to the bone tissue’s microarchitecture, leading to increased fracture risk. Several studies have provided evidence for associations between psychosocial stress and osteoporosis through various pathways, including the hypothalamic-pituitary-adrenocortical axis, the sympathetic nervous system, and other endocrine factors. As psychosocial stress provokes oxidative cellular stress with consequences for mitochondrial function and cell signaling (e.g., gene expression, inflammation), it is of interest whether extracellular vesicles (EVs) may be a relevant biomarker in this context or act by transporting substances. EVs are intercellular communicators, transfer substances encapsulated in them, modify the phenotype and function of target cells, mediate cell-cell communication, and, therefore, have critical applications in disease progression and clinical diagnosis and therapy. This review summarizes the characteristics of EVs, their role in stress and osteoporosis, and their benefit as biological markers. We demonstrate that EVs are potential mediators of psychosocial stress and osteoporosis and may be beneficial in innovative research settings.

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Exosomes as a Novel Approach to Reverse Osteoporosis: A Review of the Literature

Cited by 21 publications

References 85 publications

Exploring Quercetin Anti-Osteoporosis Pharmacological Mechanisms with In Silico and In Vivo Models

Exploring Quercetin Anti-Osteoporosis Pharmacological Mechanisms with In Silico and In Vivo Models

Morinda officinalis polysaccharide enable suppression of osteoclastic differentiation by exosomes derived from rat mesenchymal stem cells

Extracellular Vesicles: Potential Mediators of Psychosocial Stress Contribution to Osteoporosis?

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