M1 macrophage-derived exosomes aggravate bone loss in postmenopausal osteoporosis via a microRNA-98/DUSP1/JNK axis |
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Authors: | Long Yu Ming Hu Xu Cui Da Bao Zhanpeng Luo Dawei Li Litao Li Ning Liu Yunfeng Wu Xiaobo Luo Yuanzheng Ma |
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Institution: | Department of Spine Surgery, The 8th Medical Center of Chinese PLA General Hospital, Beijing, China |
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Abstract: | Macrophages (Mφs) are master regulators of the immune response and may serve as therapeutic targets in aging societies. This study aimed to determine the function of M1Mφ-exosomes (Exos) in the development of osteoporosis (OP) and the involvement of microRNA (miR)-98 and dual specificity phosphatase 1 (DUSP1). A murine model of OP was established using ovariectomies (OVX). Bone loss was observed in OVX-treated mice, as manifested by reduced bone mineral density and decreased number of bone trabecula. The bone loss was further aggravated by treatment with M1Mφ-Exos. Exos also suppressed osteogenic differentiation of MC3T3-E1 cells. miRNA microarray analysis revealed that the miR-98 level was notably upregulated in cells after Exo treatment, and DUSP1 was confirmed as a target of miR-98. Meanwhile, downregulation of miR-98 or upregulation of DUSP1 restored the osteogenic differentiation ability of MC3T3-E1 cells. In addition, upregulation of DUSP1 reduced bone loss in murine bone tissues and suppressed JNK phosphorylation. In summary, M1Mφ-derived exosomal miR-98 exacerbates bone loss and OP by downregulating DUSP1 and activating the JNK signaling pathway. miR-98 may therefore serve as a therapeutic target in OP management. |
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Keywords: | DUSP1 exosomes JNK M1 macrophages osteoporosis |
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