Pretreatment with IL-1β enhances proliferation and chondrogenic potential of synovium-derived mesenchymal stem cells

Matsumura, Etsuko; Tsuji, Kunikazu; Komori, Keiichiro; Koga, Hideyuki; Sekiya, Ichiro; Muneta, Takeshi

doi:10.1016/j.jcyt.2016.11.004

Cited by 28 publications

(25 citation statements)

References 43 publications

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“…Inflammation is thought to contribute to LF degeneration and hypertrophy. Reports have demonstrated that proinflammatory cytokines have a crucial relationship with chondrogenesis 22 , 23 . In addition, we previously demonstrated that each BMP receptor type was higher in the LF obtained from patients with LSS and segmental hypermobility 4 .…”

Section: Discussionmentioning

confidence: 99%

Mechanical stress induces elastic fibre disruption and cartilage matrix increase in ligamentum flavum

Hayashi

Suzuki

Ahmadi

et al. 2017

Sci Rep

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Lumbar spinal stenosis (LSS) is one of the most frequent causes of low back pain and gait disturbance in the elderly. Ligamentum flavum (LF) hypertrophy is the main pathomechanism of LSS, but the reason for its occurrence is not clearly elucidated. In this study, we established a novel animal model of intervertebral mechanical stress concentration and investigated the biological property of the LF. The LF with mechanical stress concentration showed degeneration with elastic fibres disruption and cartilage matrix increase, which are similar to the findings in hypertrophied LF from patients with LSS. By contrast, decreased Col2a1 expression was found in the LF at fixed levels, in which mechanical stress was strongly reduced. These findings indicate that mechanical stress plays a crucial role in LF hypertrophy through cartilage matrix increase. The findings also suggest that fusion surgery, which eliminates intervertebral instability, may change the property of the LF and lead to the relief of patients’ symptoms.

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Section: Discussionmentioning

confidence: 99%

Mechanical stress induces elastic fibre disruption and cartilage matrix increase in ligamentum flavum

Hayashi

Suzuki

Ahmadi

et al. 2017

Sci Rep

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“…Preconditioning with IL‐1β increases the expression levels of various cytokines including TNF‐α, IL‐6, IL‐8 and IL‐23A and chemokines such as CCL5, CCL20, CXCL1, CXCL3, CXCL5, CXCL6, CXCL10 and CXCL11, as well as adhesion molecules such as vascular cell adhesion molecule (VCAM)‐1, intercellular adhesion molecule (ICAM)‐1 and ICAM‐4 in MSCs, thus improving the migration ability of MSCs to the site of inflammation in vivo . In addition, IL‐1β pretreatment not only increases the proliferation but also up‐regulates the chondrogenic potential of synovial MSCs; however, high concentrations of IL‐1β exert adverse effects on synovial MSCs by reducing the adhesion ability and pluripotency . TGF‐β1, which can be released from the bone matrix, induces MSC migration into the remodelling sites and couples bone formation and resorption via the canonical SMADs signalling pathway or the non‐canonical signalling pathways involving AKT, ERK1/2, FAK and p38 .…”

Section: Trophic Factors and Cytokines For Regulation Of Msc Fatementioning

confidence: 99%

Preconditioning influences mesenchymal stem cell properties in vitro and in vivo

2018

J Cellular Molecular Medi

343

272

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Various diseases and toxic factors easily impair cellular and organic functions in mammals. Organ transplantation is used to rescue organ function, but is limited by scarce resources. Mesenchymal stem cell (MSC)‐based therapy carries promising potential in regenerative medicine because of the self‐renewal and multilineage potency of MSCs; however, MSCs may lose biological functions after isolation and cultivation for a long time in vitro. Moreover, after they are injected in vivo and migrate into the damaged tissues or organs, they encounter a harsh environment coupled with death signals due to the inadequate tensegrity structure between the cells and matrix. Preconditioning, genetic modification and optimization of MSC culture conditions are key strategies to improve MSC functions in vitro and in vivo, and all of these procedures will contribute to improving MSC transplantation efficacy in tissue engineering and regenerative medicine. Preconditioning with various physical, chemical and biological factors is possible to preserve the stemness of MSCs for further application in studies and clinical tests. In this review, we mainly focus on preconditioning and the corresponding mechanisms for improving MSC activities in vitro and in vivo; we provide a glimpse into the promotion of MSC‐based cell therapy development for regenerative medicine. As a promising consequence, MSC transplantation can be applied for the treatment of some terminal diseases and can prolong the survival time of patients in the near future.

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“…Considering stem cell therapy for OA and other joint diseases, pre-treatment or chondrogenic priming with KGN or an IL-6/Stat3 analogue, prior to the in vivo transplantation or loading onto a biomaterial scaffold, may be able to enhance the therapeutic efficacy of CSPC or MSC. [41,42] Furthermore, this study demonstrated that KGN injection could also mediate cartilage regeneration, suggesting the potential of KGN to be developed 8as clinically useful tablets. In line of this and even more importantly, the biosafety and pharmacological kinetics of the systemically and locally administrated KGN may have become the next issue to be addressed in further investigation in order to translate the small chemical to clinical application.…”

Section: Discussionmentioning

confidence: 74%

Kartogenin mediates cartilage regeneration via stimulating the IL-6/Stat3-dependent proliferation of cartilage stem/progenitor cells

Liu¹,

Li²,

Wang³

et al. 2020

Preprint

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Background: Declination of endogenous stem cells in cartilage is regarded as the cause of cartilage degeneration. Kartogenin (KGN) is well known to play an important role in chondrogenesis of mesenchymal stem cells (MSC).Methods: Using MSCs isolated from rat cartilages, we analyzed the changing of transcriptomics after the treatment of KGN in vitro. DMM animal models were then applied to identified the effect of MSCs proliferation in vivo after KGN capsule injection. Furthermore, we explored the potential mechanisms how KGN mediates cartilage regeneration and proliferation of cartilage progenitor cells.Results: In this study, we demonstrate that KGN can promote the proliferation of MSC from cartilage, respectively. The percentage of G2-M phase cells in culture reached over 10%, nearly twice as the control group with KGN treatment. Transcriptomic profiling of rat cartilage stem/progenitor cells (CSPC) revealed that the expression of at least 20 cell cycle related genes was significantly changed in response to the KGN treatment. IL-6 and its co-receptor Gp130 gene expression level are much higher than the untreated control. The phosphorylation of the IL-6-downstreamt molecular Stat-3 was enhanced upon the KGN stimulation. The knee joint injury animal model further showed the increased articular cartilage thickness after KGN treatment. Interestingly, the IHC staining also demonstrated the up-regulated level of Stat-3 phosphorylation and enhanced distribution of CD44+/CD105+ cells in the KGN-treated cartilage.Conclusion: Taken together, our data suggest that KGN promotes cartilage regeneration at least partially by stimulating the IL-6/Stat3-dependent proliferation of stem cells resident in the cartilage.

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Pretreatment with IL-1β enhances proliferation and chondrogenic potential of synovium-derived mesenchymal stem cells

Cited by 28 publications

References 43 publications

Mechanical stress induces elastic fibre disruption and cartilage matrix increase in ligamentum flavum

Mechanical stress induces elastic fibre disruption and cartilage matrix increase in ligamentum flavum

Preconditioning influences mesenchymal stem cell properties in vitro and in vivo

Kartogenin mediates cartilage regeneration via stimulating the IL-6/Stat3-dependent proliferation of cartilage stem/progenitor cells

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