Osteocalcin Alleviates Lipopolysaccharide-Induced Acute Inflammation via Activation of GPR37 in Macrophages
The G protein-coupled receptor 37 (GPR37) has been reported to be expressed in macrophages and the activation of GPR37 by its ligand/agonist, and it can regulate macrophage-associated functions and inflammatory responses. Since our previous work identified that osteocalcin (OCN) acts as an endogenou...
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MDPI AG
2022-04-01
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| Online Access: | https://www.mdpi.com/2227-9059/10/5/1006 |
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| author | Zhengjiang Qian Chunhua Liu Hongchao Li Haiyang Yang Jianhao Wu Jing Liu Yanjiao Li Xuhui Chen Jianyang Xu Xiang Li |
| author_facet | Zhengjiang Qian Chunhua Liu Hongchao Li Haiyang Yang Jianhao Wu Jing Liu Yanjiao Li Xuhui Chen Jianyang Xu Xiang Li |
| author_sort | Zhengjiang Qian |
| collection | DOAJ |
| description | The G protein-coupled receptor 37 (GPR37) has been reported to be expressed in macrophages and the activation of GPR37 by its ligand/agonist, and it can regulate macrophage-associated functions and inflammatory responses. Since our previous work identified that osteocalcin (OCN) acts as an endogenous ligand for GPR37 and can elicit various intracellular signals by interacting with GPR37, we thus hypothesized that OCN may also play a functional role in macrophage through the activation of GPR37. To verify the hypothesis, we conducted a series of in vivo and in vitro studies in lipopolysaccharide (LPS)-challenged mice and primary cultured macrophages. Our results reveal that the <i>OCN</i> gene deletion (<i>OCN</i><sup>−/−</sup>) and wild type (WT) mice showed comparable death rates and inflammatory cytokines productions in response to a lethal dose of LPS exposure. However, the detrimental effects caused by LPS were significantly ameliorated by exogenous OCN treatments in both WT and <i>OCN</i><sup>−/−</sup> mice. Notably, the protective effects of OCN were absent in <i>GPR37</i><sup>−/−</sup> mice. In coordination with the in vivo results, our in vitro studies further illustrated that OCN triggered intracellular responses via GPR37 in peritoneal macrophages by regulating the release of inflammatory factors and macrophage phagocytic function. Finally, we exhibited that the adoptive transfer of OCN-treated macrophages from WT mice significantly inhibits the release of pro-inflammatory cytokines in <i>GPR37</i><sup>−/−</sup> mice exposed to LPS. Taken together, these findings suggest a protective role of OCN against LPS-caused acute inflammation, by the activation of GPR37 in macrophages, and provide a potential application of the activation of the OCN/GPR37 regulatory axis as a therapeutic strategy for inflammatory diseases. |
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| last_indexed | 2024-03-10T03:17:15Z |
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| spelling | doaj.art-28a8a636c7b9480ab833c9a9124c6e432023-11-23T10:09:41ZengMDPI AGBiomedicines2227-90592022-04-01105100610.3390/biomedicines10051006Osteocalcin Alleviates Lipopolysaccharide-Induced Acute Inflammation via Activation of GPR37 in MacrophagesZhengjiang Qian0Chunhua Liu1Hongchao Li2Haiyang Yang3Jianhao Wu4Jing Liu5Yanjiao Li6Xuhui Chen7Jianyang Xu8Xiang Li9Guangdong Provincial Key Laboratory of Brain Connectome and Behavior, CAS Key Laboratory of Brain Connectome and Manipulation, Shenzhen Key Laboratory of Viral Vectors for Biomedicine, the Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen 518055, ChinaGuangdong Provincial Key Laboratory of Brain Connectome and Behavior, CAS Key Laboratory of Brain Connectome and Manipulation, Shenzhen Key Laboratory of Viral Vectors for Biomedicine, the Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen 518055, ChinaGuangdong Provincial Key Laboratory of Brain Connectome and Behavior, CAS Key Laboratory of Brain Connectome and Manipulation, Shenzhen Key Laboratory of Viral Vectors for Biomedicine, the Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen 518055, ChinaGuangdong Provincial Key Laboratory of Brain Connectome and Behavior, CAS Key Laboratory of Brain Connectome and Manipulation, Shenzhen Key Laboratory of Viral Vectors for Biomedicine, the Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen 518055, ChinaDepartment of Traditional Chinese Medicine, Shenzhen University General Hospital, Shenzhen 518055, ChinaDepartment of Traditional Chinese Medicine, Shenzhen University General Hospital, Shenzhen 518055, ChinaFaculty of Life and Health Sciences, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, ChinaDepartment of Neurology, Peking University Shenzhen Hospital, Shenzhen 518000, ChinaDepartment of Traditional Chinese Medicine, Shenzhen University General Hospital, Shenzhen 518055, ChinaGuangdong Provincial Key Laboratory of Brain Connectome and Behavior, CAS Key Laboratory of Brain Connectome and Manipulation, Shenzhen Key Laboratory of Viral Vectors for Biomedicine, the Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen 518055, ChinaThe G protein-coupled receptor 37 (GPR37) has been reported to be expressed in macrophages and the activation of GPR37 by its ligand/agonist, and it can regulate macrophage-associated functions and inflammatory responses. Since our previous work identified that osteocalcin (OCN) acts as an endogenous ligand for GPR37 and can elicit various intracellular signals by interacting with GPR37, we thus hypothesized that OCN may also play a functional role in macrophage through the activation of GPR37. To verify the hypothesis, we conducted a series of in vivo and in vitro studies in lipopolysaccharide (LPS)-challenged mice and primary cultured macrophages. Our results reveal that the <i>OCN</i> gene deletion (<i>OCN</i><sup>−/−</sup>) and wild type (WT) mice showed comparable death rates and inflammatory cytokines productions in response to a lethal dose of LPS exposure. However, the detrimental effects caused by LPS were significantly ameliorated by exogenous OCN treatments in both WT and <i>OCN</i><sup>−/−</sup> mice. Notably, the protective effects of OCN were absent in <i>GPR37</i><sup>−/−</sup> mice. In coordination with the in vivo results, our in vitro studies further illustrated that OCN triggered intracellular responses via GPR37 in peritoneal macrophages by regulating the release of inflammatory factors and macrophage phagocytic function. Finally, we exhibited that the adoptive transfer of OCN-treated macrophages from WT mice significantly inhibits the release of pro-inflammatory cytokines in <i>GPR37</i><sup>−/−</sup> mice exposed to LPS. Taken together, these findings suggest a protective role of OCN against LPS-caused acute inflammation, by the activation of GPR37 in macrophages, and provide a potential application of the activation of the OCN/GPR37 regulatory axis as a therapeutic strategy for inflammatory diseases.https://www.mdpi.com/2227-9059/10/5/1006osteocalcinGPR37macrophagelipopolysaccharideacute inflammation |
| spellingShingle | Zhengjiang Qian Chunhua Liu Hongchao Li Haiyang Yang Jianhao Wu Jing Liu Yanjiao Li Xuhui Chen Jianyang Xu Xiang Li Osteocalcin Alleviates Lipopolysaccharide-Induced Acute Inflammation via Activation of GPR37 in Macrophages Biomedicines osteocalcin GPR37 macrophage lipopolysaccharide acute inflammation |
| title | Osteocalcin Alleviates Lipopolysaccharide-Induced Acute Inflammation via Activation of GPR37 in Macrophages |
| title_full | Osteocalcin Alleviates Lipopolysaccharide-Induced Acute Inflammation via Activation of GPR37 in Macrophages |
| title_fullStr | Osteocalcin Alleviates Lipopolysaccharide-Induced Acute Inflammation via Activation of GPR37 in Macrophages |
| title_full_unstemmed | Osteocalcin Alleviates Lipopolysaccharide-Induced Acute Inflammation via Activation of GPR37 in Macrophages |
| title_short | Osteocalcin Alleviates Lipopolysaccharide-Induced Acute Inflammation via Activation of GPR37 in Macrophages |
| title_sort | osteocalcin alleviates lipopolysaccharide induced acute inflammation via activation of gpr37 in macrophages |
| topic | osteocalcin GPR37 macrophage lipopolysaccharide acute inflammation |
| url | https://www.mdpi.com/2227-9059/10/5/1006 |
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