Browsing by Author "Zhai, Lidong"

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    Effects of knee loading on obesity‐related nonalcoholic fatty liver disease in an ovariectomized mouse model with high fat diet
    (Wiley, 2018) Tan, Nian; Li, Xinle; Zhai, Lidong; Liu, Daquan; Li, Jie; Yokota, Hiroki; Zhang, Ping; Anatomy and Cell Biology, School of Medicine
    Aim Hormonal and nutritional disorders are the main causes of obesity and nonalcoholic fatty liver disease, especially in the elderly and postmenopausal women. Although physical activity may alleviate these disorders, the elderly may often have difficulty in conducting physical exercise. The purpose of this study was to investigate the therapeutic effect of knee loading, a new form of physical stimulation, on the symptom of obesity and fatty liver. Methods Using ovariectomized mice with high fat diet, we evaluated the effect of knee loading that applies gentle cyclic loads to the knee. Female C57BL/6 mice were divided into five groups: control (SCD), high fat diet (HF), HF with loading (HF+L), HF with ovariectomy (HF+OVX), and HF+OVX with loading (HF+OVX+L). Except for SCD, mice underwent sham operation or ovariectomy and maintained on high fat diet. After 6 weeks, the mice in HF+L and HF+OVX+L were treated with 6‐week knee loading. Results Compared to the obesity groups (HF and HF+OVX), knee loading significantly decreased a gain in body weight, liver weight, and white adipose tissue (all P<0.01). It also reduced the lipid level in the serum (P<0.01) and histological severity of hepatic steatosis (P<0.01). Furthermore, knee loading downregulated biomarkers related to the endoplasmic reticulum stress (GRP78, p‐eIF2α and ATF4) and altered biomarkers in autophagy (LC3 and p62). Conclusions Knee loading suppressed obesity‐associated metabolic alterations and hepatic steatosis, the effect with knee loading might be associated with suppression of the ER stress and promotion of autophagy.
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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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    Mechanical loading stimulates bone angiogenesis through enhancing type H vessel formation and downregulating exosomal miR-214-3p from bone marrow-derived mesenchymal stem cells
    (Wiley, 2021) Wang, Xuetong; Li, Xinle; Li, Jie; Zhai, Lidong; Liu, Daquan; Abdurahman, Abdusami; Zhang, Yifan; Yokota, Hiroki; Zhang, Ping; Biomedical Engineering, School of Engineering and Technology
    Exosomes are important transporters of miRNAs, which play varying roles in the healing of the bone fracture. Angiogenesis is one of such critical events in bone healing, and we previously reported the stimulatory effect of mechanical loading in vessel remodeling. Focusing on type H vessels and exosomal miR-214-3p, this study examined the mechanism of loading-driven angiogenesis. MiRNA sequencing and qRT-PCR revealed that miR-214-3p was increased in the exosomes of the bone-losing ovariectomized (OVX) mice, while it was significantly decreased by knee loading. Furthermore, compared to the OVX group, exosomes, derived from the loading group, promoted the angiogenesis of endothelial cells. In contrast, exosomes, which were transfected with miR-214-3p, decreased the angiogenic potential. Notably, knee loading significantly improved the microvascular volume, type H vessel formation, and bone mineral density and contents, as well as BV/TV, Tb.Th, Tb.N, and Tb.Sp. In cell cultures, the overexpression of miR-214-3p in endothelial cells reduced the tube formation and cell migration. Collectively, this study demonstrates that knee loading promotes angiogenesis by enhancing the formation of type H vessels and downregulating exosomal miR-214-3p.