Browsing by Author "Zhang, Weiwei"

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    Mechanical Loading Mitigates Osteoarthritis Symptoms by Regulating the Inflammatory Microenvironment
    (SSRN, 2021-06-14) Zhang, Weiwei; Li, Xinle; Li, Jie; Wang, Xiaoyu; Liu, Daquan; Zhai, Lidong; Ding, Beibei; Li, Guang; Sun, Yuting; Yokota, Hiroki; Zhang, Ping; Biomedical Engineering, Purdue School of Engineering and Technology
    Osteoarthritis (OA) is one of the most common chronic diseases, in which inflammatory responses in the articular cavity induce chondrocyte apoptosis and cartilage degeneration. While mechanical loading is reported to mitigate synovial inflammation, the mechanism and pathways for the loading-driven improvement of OA symptoms remain unclear. In this research, we evaluated the loading effects on the M1/M2 polarization of synovial macrophages via performing molecular, cytology, and histology analyses. In the OA groups, the cell layer of the synovial lining was enlarged with an increase in cell density. Also, M1 macrophages were polarized and pro-inflammatory cytokines were increased. In contrast, in the OA group with mechanical loading cartilage degradation was reduced and synovial inflammation was alleviated. Notably, the polarization of M1 macrophages was diminished by mechanical loading, while that of M2 macrophages was increased. Furthermore, mechanical loading decreased the levels of pro-inflammatory cytokines such as IL-1β and TNF-α and suppressed PI3K/AKT/NF-κB signaling. Consistently, NF-κB inhibited decreased the polarization of M1 macrophages in RAW264.7 macrophages. Taken together, this study demonstrates that mechanical loading changes the ratio of M1 and M2 macrophage polarization via regulating PI3K/AKT/NF-κB signaling and provides chondroprotective effects in the mouse OA model.
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    Rora Regulates Neutrophil Migration and Activation in Zebrafish
    (Frontiers Media, 2022-03-04) Hsu, Alan Y.; Wang, Tianqi; Syahirah, Ramizah; Liu, Sheng; Li, Kailing; Zhang, Weiwei; Wang, Jiao; Cao, Ziming; Tian, Simon; Matosevic, Sandro; Staiger, Christopher J.; Wan, Jun; Deng, Qing; Medical and Molecular Genetics, School of Medicine
    Neutrophil migration and activation are essential for defense against pathogens. However, this process may also lead to collateral tissue injury. We used microRNA overexpression as a platform and discovered protein-coding genes that regulate neutrophil migration. Here we show that miR-99 decreased the chemotaxis of zebrafish neutrophils and human neutrophil-like cells. In zebrafish neutrophils, miR-99 directly targets the transcriptional factor RAR-related orphan receptor alpha (roraa). Inhibiting RORα, but not the closely related RORγ, reduced chemotaxis of zebrafish and primary human neutrophils without causing cell death, and increased susceptibility of zebrafish to bacterial infection. Expressing a dominant-negative form of Rorα or disrupting the roraa locus specifically in zebrafish neutrophils reduced cell migration. At the transcriptional level, RORα regulates transmembrane signaling receptor activity and protein phosphorylation pathways. Our results, therefore, reveal previously unknown functions of miR-99 and RORα in regulating neutrophil migration and anti-microbial defense.