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KMID : 0620920230550040818
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Experimental & Molecular Medicine
2023 Volume.55 No. 4 p.818 ~ p.830
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CCL12 induces trabecular bone loss by stimulating RANKL production in BMSCs during acute lung injury
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Lee Ji-Yeon
Juan Gao
Jun Liang
Feizhen Wang
Long Xu
Jung Jun-Su
Bo He
Guangpu Liu
Ru Niu
Guangwang Liu
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Abstract
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In the last three years, the capacity of health care systems and the public health policies of governments worldwide were challenged by the spread of SARS-CoV-2. Mortality due to SARS-CoV-2 mainly resulted from the development of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Moreover, millions of people who survived ALI/ARDS in SARS-CoV-2 infection suffer from multiple lung inflammation-induced complications that lead to disability and even death. The lung-bone axis refers to the relationship between lung inflammatory diseases (COPD, asthma, and cystic fibrosis) and bone diseases, including osteopenia/osteoporosis. Compared to chronic lung diseases, the influence of ALI on the skeleton has not been investigated until now. Therefore, we investigated the effect of ALI on bone phenotypes in mice to elucidate the underlying mechanisms. In vivo bone resorption enhancement and trabecular bone loss were observed in LPS-induced ALI mice. Moreover, chemokine (C-C motif) ligand 12 (CCL12) accumulated in the serum and bone marrow. In vivo global ablation of CCL12 or conditional ablation of CCR2 in bone marrow stromal cells (BMSCs) inhibited bone resorption and abrogated trabecular bone loss in ALI mice. Furthermore, we provided evidence that CCL12 promoted bone resorption by stimulating RANKL production in BMSCs, and the CCR2/Jak2/STAT4 axis played an essential role in this process. Our study provides information regarding the pathogenesis of ALI and lays the groundwork for future research to identify new targets to treat lung inflammation-induced bone loss.
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KEYWORD
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Acute inflammation, Mechanisms of disease, Mesenchymal stem cells, Osteoporosis
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