Rescue of proinflammatory cytokine-inhibited chondrogenesis by the antiarthritic effect of melatonin in synovium mesenchymal stem cells via suppression of reactive oxygen species and matrix metalloproteinases

Liu, Xiaozhen; Xu, Yong; Chen, Sijin; Tan, Zifang; Xiong, Ke; Li, Yan; Yun, Ye‐Rang; Luo, Zong‐Ping; He, Fan; Gong, Yihong

doi:10.1016/j.freeradbiomed.2013.12.012

Cited by 72 publications

(71 citation statements)

References 53 publications

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“…Additionally, anti‐apoptotic Bcl‐2 was also downregulated in transgenic mice with COL2A1 deficiency, suggesting a possible interaction between extracellular matrix homeostasis and chondrocyte survival . Melatonin at concentration of 1 μ m reversed TNF‐ α ‐induced inhibitory effect on cell viability and anabolic factors expression in synovium mesenchymal stem cells . Moreover, Pei et al.…”

Section: Discussionmentioning

confidence: 97%

“…Melatonin exerts antioxidative, anti‐inflammatory, and immune‐enhancing effects in vitro as well as in a variety of animal species and in human . Recently, its chondroprotective effect has been suggested . Melatonin stimulates extracellular matrix synthesis of porcine articular chondrocytes in serum‐containing pellet culture system through TGF‐ β signaling pathway .…”

Section: Introductionmentioning

confidence: 99%

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Salutary effects of melatonin combined with treadmill exercise on cartilage damage

Hong

Kim²,

Lee

et al. 2014

Journal of Pineal Research

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Osteoarthritis (OA) is a major cause of disability in the adult population. The purpose of this study was to evaluate the effects of melatonin with graded dosage on extracellular matrix synthesis and cellular death in response to cartilage damage in vitro and in vivo. TNF-α reduced the viability of primary cultured chondrocytes and extracellular matrix protein, but melatonin at concentrations of 1 μm and 1 nm restored them. Rats with knee instability induced by intra-articular collagenase were used for the in vivo study. Joint parameters were significantly augmented in the collagenase injection-only group but not in the melatonin-alone or melatonin+exercise groups, as cartilage degeneration progressed. Serum TNF-α and IL-6 were upregulated by collagenase injection, which was attenuated by melatonin with and without exercise in the early phase. TGF-β1 mRNA was either conserved or enhanced by melatonin with and without exercise at the early phase. In particular, melatonin combined with exercise dramatically decreased the expression of not only catabolic mediators but also cellular death markers with lower mineralization. At the advanced phase, prolonged melatonin treatment promoted mineralization through caspase-3-mediated chondrocyte apoptosis. However, co-intervention induced extracellular matrix remodeling through increases in IL-6, EPAS-1, and MMP-13. Reconstructed micro-CT images showed that collagenase injection induced subchondral bone erosion, formation of parameniscal osteophytes, and reduction of trabecular bone thickness regardless of the intervention, which was minimized by combined intervention. In conclusion, we suggest that melatonin with treadmill exercise may have both preventive and synergistic effects on rescue from cartilage degeneration and is more effective in the initial phase.

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Salutary effects of melatonin combined with treadmill exercise on cartilage damage

Hong

Kim²,

Lee

et al. 2014

Journal of Pineal Research

View full text Add to dashboard Cite

show abstract

“…Free radicals are considered as major contributors to the secondary injury in SCI . Melatonin is a very potent free radical scavenger, and considered as the most effective lipophilic antioxidant , and thus can increase stem cell viability by suppressing reactive oxygen species . Recent studies reported that melatonin or melatonin plus exercise promotes functional recovery from SCI in rats by increasing the proliferation of endogenous NSPCs.…”

Section: Discussionmentioning

confidence: 99%

Melatonin promotes proliferation of neural stem cells from adult mouse spinal cord via the PI3K/AKT signaling pathway

Zhang

et al. 2019

FEBS Letters

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In this study, we tested the effect of melatonin on proliferation and differentiation of neural stem/progenitor cells (NSPCs) obtained from adult mouse spinal cord. We found that melatonin increases neurosphere formation from adult spinal cord NSPCs but does not alter the differentiation of the cells. Western blot results show that adult spinal cord NSPCs express both MT1 and MT2 melatonin receptors. The melatonin receptor antagonist 4P‐PDOT abrogates the melatonin‐induced neurosphere formation. Melatonin increases the phosphorylation level of protein kinase B (AKT). Blockage of phosphatidylinositol 3‐kinase (PI3K), a kinase upstream of AKT, abolishes the stimulatory effect of melatonin on spinal cord NSPCs. We conclude that melatonin promotes the proliferation of adult spinal cord NSPCs via the PI3K/AKT signaling pathway.

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“…However, when proinflammatory cytokines are present in high amounts, synovial fluid turns into an inflammatory environment, preventing chondrogenesis [19]. Depending on the level of proinflammatory cytokines, inflammatory synovial fluid could be more or less harmful for chondrogenesis and cartilage matrix formation ( i.e.…”

Section: Discussionmentioning

confidence: 99%

Inflammation affects the viability and plasticity of equine mesenchymal stem cells: possible implications in intra-articular treatments

et al. 2017

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Mesenchymal stem cells (MSCs) are gaining relevance for treating equine joint injuries because of their ability to limit inflammation and stimulate regeneration. Because inflammation activates MSC immunoregulatory function, proinflammatory priming could improve MSC efficacy. However, inflammatory molecules present in synovial fluid or added to the culture medium might have deleterious effects on MSCs. Therefore, this study was conducted to investigate the effects of inflammatory synovial fluid and proinflammatory cytokines priming on viability and plasticity of equine MSCs. Equine bone marrow derived MSCs (eBM-MSCs) from three animals were cultured for 72 h in media supplemented with: 20% inflammatory synovial fluid (SF); 50 ng/mL IFN-γ and TNF-α (CK50); and 20 ng/mL IFN-γ and TNF-α (CK20). Proliferation assay and expression of proliferation and apoptosis-related genes showed that SF exposed-eBM-MSCs maintained their viability, whereas the viability of CK primed-eBM-MSCs was significantly impaired. Tri-lineage differentiation assay revealed that exposure to inflammatory synovial fluid did not alter eBM-MSCs differentiation potential; however, eBM-MSCs primed with cytokines did not display osteogenic, adipogenic or chondrogenic phenotype. The inflammatory synovial environment is well tolerated by eBM-MSCs, whereas cytokine priming negatively affects the viability and differentiation abilities of eBM-MSCs, which might limit their in vivo efficacy.

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Rescue of proinflammatory cytokine-inhibited chondrogenesis by the antiarthritic effect of melatonin in synovium mesenchymal stem cells via suppression of reactive oxygen species and matrix metalloproteinases

Cited by 72 publications

References 53 publications

Salutary effects of melatonin combined with treadmill exercise on cartilage damage

Salutary effects of melatonin combined with treadmill exercise on cartilage damage

Melatonin promotes proliferation of neural stem cells from adult mouse spinal cord via the PI3K/AKT signaling pathway

Inflammation affects the viability and plasticity of equine mesenchymal stem cells: possible implications in intra-articular treatments

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