Cordycepin promotes osteogenesis of bone marrow-derived mesenchymal stem cells and accelerates fracture healing via hypoxia in a rat model of closed femur fracture

Li, Zhengzhao; Gu, Yue; Lin, Zhiwei; Ma, Hongfei; Zhang, Shunli

doi:10.1016/j.biopha.2020.109991

Cited by 13 publications

(10 citation statements)

References 28 publications

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“…Rehabilitation of extensive bone defects is a formidable challenge in modern medical science. However, owing to their outstanding capacity for bringing about osteogenic differentiation, bone marrow mesenchymal stem cells (BMSCs) have become the osteogenous seed cells of bone tissue engineering and cytotherapy in recent years ( Li Z. et al, 2020 ; Sui et al, 2019 ). The regeneration activities of BMSCs may be attributed to the diverse mechanisms of molecular cross-talk between BMSCs and adjacent cells ( Thurairajah et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Macrophage-Derived Exosomes Promote Bone Mesenchymal Stem Cells Towards Osteoblastic Fate Through microRNA-21a-5p

Liu

Luo

et al. 2022

Front. Bioeng. Biotechnol.

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The effective healing of a bone defect is dependent on the careful coordination of inflammatory and bone-forming cells. In the current work, pro-inflammatory M1 and anti-inflammatory M2 macrophages were co-cultured with primary murine bone mesenchymal stem cells (BMSCs), in vitro, to establish the cross-talk among polarized macrophages and BMSCs, and as well as their effects on osteogenesis. Meanwhile, macrophages influence the osteogenesis of BMSCs through paracrine forms such as exosomes. We focused on whether exosomes of macrophages promote osteogenic differentiation. The results indicated that M1 and M2 polarized macrophage exosomes all can promote osteogenesis of BMSCs. Especially, M1 macrophage-derived exosomes promote osteogenesis of BMSCs through microRNA-21a-5p at the early stage of inflammation. This research helps to develop an understanding of the intricate interactions among BMSCs and macrophages, which can help to improve the process of bone healing as well as additional regenerative processes by local sustained release of exosomes.

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Section: Introductionmentioning

confidence: 99%

Macrophage-Derived Exosomes Promote Bone Mesenchymal Stem Cells Towards Osteoblastic Fate Through microRNA-21a-5p

Liu

Luo

et al. 2022

Front. Bioeng. Biotechnol.

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“…In this study, we identified the main active components of HPASD through UPLC/Q-TOF MS analysis combined with database retrieval. Among these active components, Cordycepin ( Li et al, 2020 ), Chlorogenic acid ( Liu L. et al, 2018 ), Puerarin ( Wong and Rabie, 2007 ), Hyperin ( Saul et al, 2021 ) and Naringenin ( Estai et al, 2011 ) have been proved to promote fracture healing. Meanwhile, these active ingredients can also improve TBI ( Wang et al, 2014 ; Deng et al, 2021 ; Wei et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Hu’po Anshen Decoction Accelerated Fracture-Healing in a Rat Model of Traumatic Brain Injury Through Activation of PI3K/AKT Pathway

Shen

Yao

et al. 2022

Front. Pharmacol.

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Hu’po Anshen decoction (HPASD) is a traditional Chinese medicine formula comprising five herbal medicines for the treatment of concussion and fracture healing, but its pharmacological mechanism is still unclear. Ultra-performance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UPLC/Q-TOF MS) was used to analyze the main active components of HPASD. Rats were randomly assigned to fracture group, fracture combined with traumatic brain injury (TBI) group (FBI) and FBI combined with HPASD treatment group (FBIH). Rats in the FBIH group were given oral doses of HPASD (2.4 g/kg, 4.8 g/kg and 9.6 g/kg) for 14 or 21 consecutive days. The fracture callus formation and fracture sites were determined by radiographic analysis and micron-scale computed tomography (micro-CT) analysis. Hematoxylin and eosin (H&E) staining and a three-point bending test were applied to assess histological lesions and biomechanical properties, respectively. The levels of cytokines-/protein-related to bone formation and differentiation as well as PI3K/AKT pathway-related proteins were determined by Enzyme-linked immunosorbent assay (ELISA), quantitative reverse transcription-polymerase chain reaction (qRT-PCR), or western blot assays, respectively. UPLC-Q/TOF-MS-based serum metabolomic analysis was also performed to investigate the therapeutic effects of HPASD in the treatment of FBI. UPLC/Q-TOF MS analysis showed the chemical components in HPASD, including flavonoids, amino acids, saponins, and phenylpropanoid constituents, etc. HPASD dose-dependently promoted callus formation, increased bone density, improved mechanical parameters and morphological scores, and facilitated the expressions of VEGF, PDGF, bFGF, VEGFA, CoL1A1, RUNX2, BMP2, and Aggrecan, inhibited the expression of MMP13, and activated PI3K/AKT pathway. Metabolomics analysis revealed abnormalities of malate-aspartate shuttle and glucose-alanine. HPASD accelerates fracture healing by promoting bone formation and regulating the malate-aspartate shuttle and glucose-alanine cycle, which might be associated with the activation of the PI3K/AKT pathway.

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“…Cordycepin may have applications in bone regeneration [ 9 ]. Yu et al [ 10 ] reported on the dual role of Cordycepin.…”

Section: Discussionmentioning

confidence: 99%

Dose-Dependent Effect of Cordycepin on Viability, Proliferation, Cell Cycle, and Migration in Dental Pulp Stem Cells

Boreak

Alkahtani

Alzahrani

et al. 2021

JPM

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Objective: To examine the effect of Cordycepin on the viability, proliferation, and migratory properties of dental pulp-derived mesenchymal stem cells. Materials and methods: The pulp was derived from human premolar teeth extracted for orthodontic purposes after obtaining informed consent. The samples were transferred to the laboratory for processing. DPSCs were expanded and characterized using flow cytometry and differentiation to the bone, adipose, and cartilage cells was examined. MTT Assay was performed using various concentrations of Cordycepin. The growth curve was plotted for 13 days. Cell cycle analysis was performed by flow cytometry. Migratory ability was assessed by wound healing assay. ROS generation was detected by flow cytometry. Gene expression was quantified by RT-qPCR. Statistical analysis was performed. p < 0.05 was considered as significant and p < 0.01 was considered as highly significant (* p < 0.05, and ** p < 0.01). Results: DPSCs expressed characteristic MSC-specific markers and trilineage differentiation. Cordycepin at lower concentrations did not affect the viability of DPSCs. The growth curve of cells showed a dose-dependent increase in cell numbers till the maximum dose. DPSCs treated with 2.5 µM Cordycepin was found to have a reduced G1 phase cell percentage. DPSCs treated with 2.5 µM and 5 µM Cordycepin showed a significant decrease in G2 phase cells. No significant difference was observed for S phase cells. Cordycepin treatment affected the migratory ability in DPSCs in a concentration-dependent manner. Conclusion: Cordycepin can be used at therapeutic doses to maintain stem cells.

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Cordycepin promotes osteogenesis of bone marrow-derived mesenchymal stem cells and accelerates fracture healing via hypoxia in a rat model of closed femur fracture

Cited by 13 publications

References 28 publications

Macrophage-Derived Exosomes Promote Bone Mesenchymal Stem Cells Towards Osteoblastic Fate Through microRNA-21a-5p

Macrophage-Derived Exosomes Promote Bone Mesenchymal Stem Cells Towards Osteoblastic Fate Through microRNA-21a-5p

Hu’po Anshen Decoction Accelerated Fracture-Healing in a Rat Model of Traumatic Brain Injury Through Activation of PI3K/AKT Pathway

Dose-Dependent Effect of Cordycepin on Viability, Proliferation, Cell Cycle, and Migration in Dental Pulp Stem Cells

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