Cordycepin inhibits chondrocyte hypertrophy of mesenchymal stem cells through PI3K/Bapx1 and Notch signaling pathway

Cao, Zhen; Dou, Ce; Li, Jianmei; Tang, Xiangyu; Xiang, Junyu; Zhao, Chunrong; Zhu, Lingyu; Bai, Yun; Xiang, Qiang

doi:10.5483/bmbrep.2016.49.10.071

Cited by 20 publications

(15 citation statements)

References 39 publications

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“…The role of hedgehog proteins in the regulation of chondrogenic differentiation and chondrogenesis has been previously established [10, 20, 21]. However, activation of hedgehog signaling also promotes chondrocyte hypertrophy and ossification during chondrogenesis, while hypertrophic differentiation and pathologic responses can affect the formation of stable hyaline cartilage [11, 12, 22, 23]. In this study, we demonstrated that chondrogenic hypertrophy and aging were markedly alleviated when chondrogenesis was induced in a microgravity culture environment.…”

Section: Discussionsupporting

confidence: 53%

Chondrogenic differentiation of bone marrow-derived mesenchymal stem cells following transfection with Indian hedgehog and sonic hedgehog using a rotary cell culture system

Chen

Liu

et al. 2019

Cell Mol Biol Lett

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Background Indian hedgehog (IHH) and Sonic hedgehog (SHH) are important regulators of chondrogenesis. However, activation of IHH and SHH also promotes chondrocyte hypertrophy and ossification during chondrogenesis. The aims of this study were to investigate the effect of microgravity on IHH- and SHH-induced chondrogenic differentiation and to elucidate the role of microgravity in this process. Methods Adenovirus plasmids encoding the rabbit IHH gene and SHH genes were constructed in vitro and transfected into rabbit bone marrow-derived mesenchymal stem cells (BMSCs). A rotary cell culture system (RCCS), in which a dynamic three-dimensional culture system combines the mechanical environment with a three-dimensional culture surface, was used for cell culture and differentiation. During the induction of differentiation, expression levels of cartilage-related and cartilage hypertrophy-related genes and proteins were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting, respectively. Toluidine blue and collagen II immunohistochemical staining and annexin V-Cy3 staining were used to indicate investigate cartilage matrix synthesis and hypertrophic hypertrophy, respectively, on day 21 after induction of differentiation. Results In this study, IHH and SHH were shown to be equipotent inducers of chondrogenesis in rabbit BMSCs, as evidenced by strong staining for proteoglycans and collagen II, and increased expression of mRNAs and proteins associated with chondrogenesis in an RCCS environment. More importantly, chondrogenic hypertrophy and aging were effectively inhibited in the RCCS environment. In addition, levels of cartilage-related markers in the IHH and SHH transfection groups were initially increased and later decreased in the traditional two-dimensional environment, while cartilage hypertrophy-related factors revealed higher mRNA expression levels during induction. Conclusions In summary, microgravity significantly promoted chondrogenic differentiation of BMSCs induced by IHH and SHH and attenuated chondrogenic hypertrophy and aging during chondrogenesis. Furthermore, exogenous IHH and SHH had the same effect on chondrogenic differentiation of BMSCs in the RCCS environment. This study provides further evidence of chondrogenic induction of BMSCs in vitro via IHH and SHH gene delivery. Electronic supplementary material The online version of this article (10.1186/s11658-019-0144-2) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 53%

Chondrogenic differentiation of bone marrow-derived mesenchymal stem cells following transfection with Indian hedgehog and sonic hedgehog using a rotary cell culture system

Chen

Liu

et al. 2019

Cell Mol Biol Lett

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“…Studies have shown that 1 μg/mL of cordycepin can promote the differentiation of MCSs into cartilage and increase the expression levels of intracellular cartilage genes. Further experiments have demonstrated that this phenomenon is mediated by the inhibition of Nrf2 and the activation of BMP signaling[59]. Similarly, some scholars have found that lactoferrin promotes early chondrogenic differentiation of ATDC5 cells by the activating Smad2/3-Sox9 signaling pathway while also exhibiting osteoinductive effects, and also inhibits excessive hypertrophy of chondrocytes[60].…”

Section: Effects Of Various Antimicrobial Agents On Chondrogenic Diffmentioning

confidence: 99%

Effects of various antimicrobial agents on multi-directional differentiation potential of bone marrow-derived mesenchymal stem cells

Li¹,

Yue²

2019

WJSC

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Antimicrobial drugs of several classes play an important role in the treatment of bone and joint infections. In addition to fighting pathogenic microorganisms, the effects of drugs on local tissues and cells are also related to the course and prognosis of bone and joint infections. The multi-directional differentiation potential of bone marrow-derived mesenchymal stem cells (MSCs) is essential for tissue repair after local injury, which is directly related to the recovery of bone, cartilage, and medullary adipose tissue. Our previous studies and the literature indicate that certain antimicrobial agents can regulate the differentiation potential of bone marrow-derived MSCs. Here, in order to systematically analyze the effects of various antimicrobial drugs on local tissue regeneration, we comprehensively review the studies on the effects of these drugs on MSC differentiation, and classify them according to the three differentiation directions (osteogenesis, chondrogenesis, and adipogenesis). Our review demonstrates the specific effects of different antimicrobial agents on bone marrow-derived MSCs and the range of concentrations at which they work, and provides a basis for drug selection at different sites of infection.

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“…Previous work revealed that COR protects against osteoporosis as a result of increased bone generation and inhibited bone loss (Figure 4 and Table S5). Mechanistically, COR alleviates osteonecrosis via a decrease in ROS [110], protects the femoral head from alcohol-induced injury by activating β-catenin and Runx2 [111] and induces chondrogenesis through the stimulation of PI3K and MMP-13 [112].…”

Section: Other Medicinal Values and Biological Applicationsmentioning

confidence: 99%

Therapeutic Potential and Biological Applications of Cordycepin and Metabolic Mechanisms in Cordycepin-Producing Fungi

Qin

Yang

et al. 2019

Molecules

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Cordycepin (3′-deoxyadenosine), a cytotoxic nucleoside analogue found in Cordyceps militaris, has attracted much attention due to its therapeutic potential and biological value. Cordycepin interacts with multiple medicinal targets associated with cancer, tumor, inflammation, oxidant, polyadenylation of mRNA, etc. The investigation of the medicinal drug actions supports the discovery of novel targets and the development of new drugs to enhance the therapeutic potency and reduce toxicity. Cordycepin may be of great value owing to its medicinal potential as an external drug, such as in cosmeceutical, traumatic, antalgic and muscle strain applications. In addition, the biological application of cordycepin, for example, as a ligand, has been used to uncover molecular structures. Notably, studies that investigated the metabolic mechanisms of cordycepin-producing fungi have yielded significant information related to the biosynthesis of high levels of cordycepin. Here, we summarized the medicinal targets, biological applications, cytotoxicity, delivery carriers, stability, and pros/cons of cordycepin in clinical applications, as well as described the metabolic mechanisms of cordycepin in cordycepin-producing fungi. We posit that new approaches, including single-cell analysis, have the potential to enhance medicinal potency and unravel all facets of metabolic mechanisms of cordycepin in Cordyceps militaris.

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Cordycepin inhibits chondrocyte hypertrophy of mesenchymal stem cells through PI3K/Bapx1 and Notch signaling pathway

Cited by 20 publications

References 39 publications

Chondrogenic differentiation of bone marrow-derived mesenchymal stem cells following transfection with Indian hedgehog and sonic hedgehog using a rotary cell culture system

Chondrogenic differentiation of bone marrow-derived mesenchymal stem cells following transfection with Indian hedgehog and sonic hedgehog using a rotary cell culture system

Effects of various antimicrobial agents on multi-directional differentiation potential of bone marrow-derived mesenchymal stem cells

Therapeutic Potential and Biological Applications of Cordycepin and Metabolic Mechanisms in Cordycepin-Producing Fungi

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