HighlightsOxidative stress in the arthritis joint is involved in generating mediators for inflammation.Oxidative stress-induced expression of Cox-2 was mediated by MAPKs and NF-κB.ROS-induced MAPKs and NF-κB were attenuated by inhibition of MAPKKK TAK1.Inhibition of TAK1 activity resulted in reduced expression of Cox-2 and PGE2.ROS-induced TAK1 activation and Cox-2 expression was inhibited by antioxidants N-acetyl cysteamine and hyaluronic acid.

Despite recent cell-engineering advances, treatment and repair of cartilage remains challenging. Although stem cell transplantation therapy using mesenchymal stem cells (MSCs) is considered a prominent strategy, the major problem of limited proliferative capacity of autologous cells has been unsolved. Recently, an induced pluripotent stem (iPS) cell line was suggested as an alternative way to cure various human diseases due to their potential proliferating infinitely while possessing the capacity to form all types of cells. However, the method to induce lineage-restricted differentiation has not been well examined or established. Here, we suggest a simple method to induce mesenchymal progenitors possessing chondrogenic property from mouse iPS cells. The MSC-like cells produced in our study expressed some MSC markers, and could also differentiate to osteoblast and adipocyte. The present study demonstrates the property of iPS cells as an alternative candidate for treatment of articular disorders, and suggests an effective approach for preparing chondrocyte from iPS cells.

SummaryInflammation‐induced reactive oxygen species (ROS) are implicated in cellular dysfunction and an important trigger for aging‐ or disease‐related tissue degeneration. Inflammation‐induced ROS in stem cells lead to deterioration of their properties, altering tissue renewal or regeneration. Pathological ROS generation can be induced by multiple steps, and dysfunction of antioxidant systems is a major cause. The identification of the central molecule mediating the above‐mentioned processes would pave the way for the development of novel therapeutics for aging, aging‐related diseases, or stem cell therapies. In recent years, microRNAs (miRNAs) have been shown to play important roles in many biological reactions, including inflammation and stem cell functions. In inflammatory conditions, certain miRNAs are highly expressed and mediate some cytotoxic actions. Here, we focused on miR‐155, which is one of the most prominent miRNAs in inflammation and hypothesized that miR‐155 participates to inflammation‐induced ROS generation in stem cells. We observed mesenchymal stem cells (MSCs) from 1.5‐year‐old aged mice and determined that antioxidants, Nfe2l2, Sod1, and Hmox1, were suppressed, while miR‐155‐5p was highly expressed. Subsequent in vitro studies demonstrated that miR‐155‐5p induces ROS generation by suppression of the antioxidant genes by targeting the common transcription factor C/ebpβ. Moreover, this mechanism occurred during the cell transplantation process, in which ROS generation is triggering loss of transplanted stem cells. Finally, attenuation of antioxidants and ROS accumulation were partially prevented in miR‐155 knockout MSCs. In conclusion, our study suggests that miR‐155 is an important mediator connecting aging, inflammation, and ROS generation in stem cells.

HighlightsHyaluronic acid (HA) has a pharmacological role for reduction of cellular superoxide.In HA-treated chondrocytes, expression of Nrf2 and its downstream genes was upregulated.Inhibition of Akt or suppression of HA receptors prevented HA-mediated Nrf2 accumulation.Nrf2 siRNA inhibited the HA effect on antioxidant enzymes.HA might contribute to ROS reduction through Nrf2 regulation by activating Akt.

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