MiR-19b-3p Attenuates Chondrocytes Injury by Inhibiting MAPK/NF-Κb Axis via Targeting SOCS1.

In this study, miR-19b-3p was downregulated in osteoarthritic cartilage tissues and IL-1ß-stimulated primary chondrocytes, and miR-19b-3p overexpression reversed the inhibitory effect of IL-1ß on cell viability, the promotion effects of apoptosis, inflammatory factor secretion and extracellular matrix degradation, whereas the opposite effect was observed with miR-19b-3p inhibitor. Moreover, SOCS1 is a target gene of miR-19b-3p. Furthermore, SOCS1 overexpression enhanced cell injury compared with IL-1ß alone treatment, whereas knockdown of SOCS1 restored cell damage caused by IL-1ß. Further studies revealed that miR-19b-3p promoted chondrocyte injury repair by suppressing SOCS1 expression, and we found that was mediated by blocking the MAPK/NF-κB axis. Taken together, our findings may provide a new therapeutic strategy for osteoarthritis.

Inhibiting the aberrant activation of Wnt/ß-catenin signaling by selenium supplementation ameliorates deoxynivalenol-induced toxicity and catabolism in chondrocytes.

Kashin-Beck disease (KBD) is an endemic degenerative osteoarticular disorder associated with physical disability and a heavy economic burden. Contamination by mycotoxin deoxynivalenol (DON) and selenium deficiency have been proposed to be key etiological factors for KBD, and can work together to aggravate the progression of KBD. Nevertheless, the mechanism of DON in KBD remains elusive. In the present study, exposure to DON dose-dependently suppressed cell viability and expression of pro-proliferation marker PCNA in human chondrocytes, whereas it enhanced lactate dehydrogenase release, cell apoptosis, and caspase-3/9 activity. In addition, DON incubation shifted metabolism homeostasis towards catabolism by suppressing the transcription of collagen II and aggrecan, and the production of sulphated glycosaminoglycans and TIMP-1, while increasing matrix metalloproteinase levels (MMP-1 and MMP-13). Mechanistically, DON exposure induced the activation of Wnt/ß-catenin signaling. Intriguingly, blocking this pathway reversed the adverse effects of DON on cytotoxic damage and metabolism disruption to catabolism. Notably, supplementation with selenium reduced DON-induced activation of the Wnt/ß-catenin pathway. Moreover, selenium addition abrogated cytotoxic injury and excessive pro-catabolic gene expression in chondrocytes upon DON conditions. These findings confirm that DON may facilitate the development of KBD by inducing cell injury, inhibiting matrix synthesis, and increasing cellular catabolism by activating the Wnt/ß-catenin signaling, which were partially reversed by selenium supplementation. Thus, the current study may presents a new viewpoint for how selenium supplementation ameliorates the development of KBD by inhibiting DON-induced cytotoxic injury and metabolism imbalance in chondrocytes.