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Browsing by Subject "Vessel remodeling"
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Item Knee loading protects against osteonecrosis of the femoral head by enhancing vessel remodeling and bone healing(Elsevier, 2015-12) Liu, Daquan; Li, Xinle; Li, Jie; Yang, Jing; Yokota, Hiroki; Zhang, Ping; Department of Biomedical Engineering, School of Engineering and TechnologyOsteonecrosis of the femoral head is a serious orthopedic problem. Moderate loads with knee loading promote bone formation, but their effects on osteonecrosis have not been investigated. Using a rat model, we examined a hypothesis that knee loading enhances vessel remodeling and bone healing through the modulation of the fate of bone marrow-derived cells. In this study, osteonecrosis was induced by transecting the ligamentum teres followed by a tight ligature around the femoral neck. For knee loading, 5 N loads were laterally applied to the knee at 15 Hz for 5 min/day for 5 weeks. Changes in bone mineral density (BMD) and bone mineral content (BMC) of the femur were measured by pDEXA, and ink infusion was performed to evaluate vessel remodeling. Femoral heads were harvested for histomorphometry, and bone marrow-derived cells were isolated to examine osteoclast development and osteoblast differentiation. The results showed that osteonecrosis significantly induced bone loss, and knee loading stimulated both vessel remodeling and bone healing. The osteonecrosis group exhibited the lowest trabecular BV/TV (p b 0.001) in the femoral head, and lowest femoral BMD and BMC (both p b 0.01). However, knee loading increased trabecular BV/TV (p b 0.05) as well as BMD (pb 0.05) and BMC (p b 0.01). Osteonecrosis decreased the vessel volume (pb 0.001), vessel number (pb 0.001) and VEGF expression (p b 0.01), and knee loading increased them (pb 0.001, pb 0.001 and p b 0.01). Osteonecrosis activated osteoclast development, and knee loading reduced its formation, migration, adhesion and the level of “pit” formation (pb 0.001, pb 0.01, pb 0.001 and pb 0.001). Furthermore, knee loading significantly increased osteoblast differentiation and CFU-F (both p b 0.001). A significantly positive correlation was observed between vessel remodeling and bone healing (both p b 0.01). These results indicate that knee loading could be effective in repair osteonecrosis of the femoral head in a rat model. This effect might be attributed to promoting vessel remodeling, suppressing osteoclast development, and increasing osteoblast and fibroblast differentiation. In summary, the current study suggests that knee loading might potentially be employed as a non-invasive therapy for osteonecrosis of the femoral head.Item 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 TechnologyExosomes 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.