Melatonin rescued interleukin 1β-impaired chondrogenesis of human mesenchymal stem cells
Chondrogenesis
DOI:
10.1186/s13287-018-0892-3
Publication Date:
2018-06-13T21:42:38Z
AUTHORS (15)
ABSTRACT
Osteoarthritis (OA) is a widespread arthritic disease and primary cause of disability. Increasing evidence suggests that inflammation has pivotal part in its pathogenesis. Interleukin-1β (IL-1β) mediator local inflammatory processes OA. Current therapies for OA mainly focus on the symptoms advanced stage disease. The possible utilization bone marrow mesenchymal stem cells (BMSCs) to regenerate cartilage an appealing method, but case requires chondrogenesis take place within inflamed environment. Our previous study showed melatonin (MLT) can promote chondrogenic differentiation MSCs, whether MLT rescue IL-1β-impaired human BMSCs not yet been established. MLT, which have anti-inflammatory prochondrogenic effects, demonstrated potential defeating IL-1β-induced inhibition further should be conducted. Human marrow-derived MSCs were separated cultured based our system was already documented. A high-density micromass culture used BMSCs, also described previously. induced 7, 14, 21 days with treatment IL-1β MLT. pellets then evaluated by morphology, extracellular matrix accumulation, chondrogenic, metabolic, apoptotic marker expression. Furthermore, cell apoptosis assessed TUNEL assay. phosphorylation level P65 IκBα NF-κB pathway activity explored day BMSCs. current evaluation save different aspects. Firstly, restore pellet size, synthesis accumulation. Secondly, upregulate COL2A1 expression at both mRNA protein levels, regulate levels other markers like ACAN, SOX9, COL10A1 presence IL-1β. Thirdly, maintain metabolic balance process suppressing catabolic genes, such as MMP, MMP13, ADAMTS4. subdue throughout chondrogenesis. Meanwhile, suppressed IκBα, elevated treatment, indicating attenuate activation signaling. restoring size maintaining balance, reducing apoptosis. signaling pathway, most important downstream IL-1β, plays crucial role inflammation, apoptosis, metabolism. Thus, prospects treating due multifaceted functions, mitigating
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