Naringin promotes cellular chemokine synthesis and potentiates mesenchymal stromal cell migration via the Ras signaling pathway

Lin, Feng; Zhu, Yuan Xiao; Hu, Gangfeng

doi:10.3892/etm.2018.6634

Cited by 13 publications

(13 citation statements)

References 41 publications

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“…28 Lin et al demonstrated that the Ras family was remarkably activated by naringin. 29 Furthermore, the ERK 1/2 pathway can regulate osteogenic differentiation through microRNA. 30 Meanwhile, GelMA hydrogels and collagen have also been demonstrated to regulate the osteogenic differentiation of MSCs via ERK signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

Controlled Release of Naringin in GelMA-Incorporated Rutile Nanorod Films to Regulate Osteogenic Differentiation of Mesenchymal Stem Cells

et al. 2019

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Naringin, a Chinese herbal medicine, has been demonstrated to concentration-dependently promote osteogenic differentiation of mesenchymal stem cells (MSCs). However, it remains a challenge to load naringin on coatings for osteogenesis and further control the release kinetics. Here, we demonstrated that the release behavior of naringin on rutile nanorod films could be controlled by either mixing naringin with gelatin methacryloyl (GelMA) before spinning onto the films or soaking the obtained GelMA-incorporated films with the naringin solution to achieve the distinct degradation-type release and diffusion-type release, respectively. We further revealed that the naringin-loaded coatings facilitated adhesion, proliferation and late differentiation, and mineralization of MSCs. Our findings provided a novel strategy to engineer the coatings with controlled release of naringin and emphasized the bioactivity of naringin for the osteogenic differentiation of MSCs.

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Section: Discussionmentioning

confidence: 99%

Controlled Release of Naringin in GelMA-Incorporated Rutile Nanorod Films to Regulate Osteogenic Differentiation of Mesenchymal Stem Cells

et al. 2019

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“…Moreover, total flavonoids of DR could promote osteogenic differentiation of rat dental pulp stem cells via the PI3K/Akt pathway [42]. Lin et al found that the effect of naringin on the healing of fracture may be related to the promotion of the synthesis and secretion of cellular chemokines (CXCL5, CXCL6) and enhancement of mesenchymal stromal cell migration through Ras signaling pathway [43]. In addition, naringin stimulates angiogenesis by regulating the VEGF/VEGFR-2 signaling pathway in rats, thereby promoting fracture healing [38].…”

Section: Discussionmentioning

confidence: 99%

Identified the Synergistic Mechanism of Drynariae Rhizoma for Treating Fracture Based on Network Pharmacology

Lin

Wang

et al. 2019

Evidence-Based Complementary and Alternative Medicine

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Background Drynariae Rhizoma (DR) has been widely used in the prevention and treatment of various fractures. However, the specific mechanisms of DR's active ingredients have not been elucidated. The purpose of this study was to explore the synergistic mechanisms of DR for treating fracture. Methods A network pharmacology approach integrating ingredient screening, target exploration, active ingredients-gene target network construction, protein-protein interaction network construction, molecular docking, gene-protein classification, gene ontology (GO) functional analysis, KEGG pathway enrichment analysis, and signaling pathway integration was used. Results This approach identified 17 active ingredients of DR, interacting with 144 common gene targets and 143 protein targets of DR and fracture. NCOA1, GSK3B, TTPA, and MAPK1 were identified as important gene targets. Five most important protein targets were also identified, including MAPK1, SRC, HRAS, RXRA, and NCOA1. Molecular docking found that DR has a good binding potential with common protein targets. GO functional analysis indicated that common genes involve multiple processes, parts and functions in biological process, cellular component, and molecular function, including positive regulation of transcription from RNA polymerase II promoter, signal transduction, cytosol, extracellular exosome, cytoplasm, and protein binding. The KEGG pathway enrichment analysis indicated that common gene targets play a role in repairing fractures in multiple signaling pathways, including MAPK, PI3K/AKT, Ras, and VEGF signaling pathways. MAPK and PI3K/AKT signaling pathways were involved in osteoblast formation, Ras signaling pathway was involved in enhancing mesenchymal stromal cell migration, and VEGF signaling pathway was involved in angiogenesis. Conclusion The study revealed the correlation between DR and fracture and the potential synergistic mechanism of different targets of DR in the treatment of fractures, which provides a reference for the development of new drugs.

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“…Currently, researchers have been focused on improving the condition for MSC recruitment by using biological agents. Clinical-standard platelet products loaded membranes [7] and naringin [8] successfully support MSC colony formation and promote MSC migration in vitro.…”

Section: Introductionmentioning

confidence: 94%

Short Wave Enhances Mesenchymal Stem Cell Recruitment through Hypoxia-Inducible Factor-1 Signaling in Fracture Healing

Chen

Wang³

et al. 2020

Preprint

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Background: As a type of high-frequency electrotherapy, a short wave can promote the fracture healing process; yet, its underlying therapeutic mechanisms still remain unclear.Purpose: To observe the effect of short wave on mesenchymal stem cell (MSC) homing and its mechanisms associated with fracture healing.Materials and Methods: The effect of short wave on a fracture healing was examined in 40 rats. Stabilized femur fractures were established by intramedullary fixation; radiography was used to analyze the morphology and micro-architecture of the callus. Additionally, fluorescence assays were used to analyze the MSC migration after treatment in 20 nude mice with a femoral fracture. For in vitro study, osteoblast simulated fracture site was first irradiated by the short wave; siRNA targeting HIF-1 was used to investigate the role of HIF-1. Osteoblast cultured supernatant was then collected as chemotaxis content of MSC, and the migration of MSC was evaluated using wound healing assay and trans-well chamber test. The expression of HIF-1 and its related factors were quantified by qRT-PCR, ELISA, and Western blot.Results: Our in vivo experiment indicated that short wave could promote MSC migration, increase local and serum HIF-1 levels, induce changes in callus formation, and improve callus microarchitecture and mechanical properties, thus speeding up the healing process of the fracture site. Moreover, the in vitro results further indicated that short waves upregulated HIF-1 expression in osteoblast and increased HIF-1, SDF-1 protein levels in the supernatant, as well as the expression of CXCR-4, β-catenin, F-actin and phosphorylation levels of FAK in MSC. On the other hand, the inhibition of HIF-1α was significantly restrained by the inhibition of HIF-1α in osteoblast and it partially inhibited the migration of MSC.Conclusions: These results suggested that short wave could increase HIF-1 in callus, which is one of the crucial mechanisms of chemotaxis MSC homing in fracture healing.

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Naringin promotes cellular chemokine synthesis and potentiates mesenchymal stromal cell migration via the Ras signaling pathway

Cited by 13 publications

References 41 publications

Controlled Release of Naringin in GelMA-Incorporated Rutile Nanorod Films to Regulate Osteogenic Differentiation of Mesenchymal Stem Cells

Controlled Release of Naringin in GelMA-Incorporated Rutile Nanorod Films to Regulate Osteogenic Differentiation of Mesenchymal Stem Cells

Identified the Synergistic Mechanism of Drynariae Rhizoma for Treating Fracture Based on Network Pharmacology

Short Wave Enhances Mesenchymal Stem Cell Recruitment through Hypoxia-Inducible Factor-1 Signaling in Fracture Healing

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