CCL12 induces trabecular bone loss by stimulating RANKL production in BMSCs during acute lung injury
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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.
Abstract
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.
참고문헌 (45)
- Swenson, K. E., "Pathophysiology of acute respiratory distress syndrome and COVID-19 lung injury", Crit. Care Clin, 37, pp.749~776 (2021)
- Torres Acosta, M. A., "Pathogenesis of COVID-19-induced ARDS:implications for an ageing population", Eur. Respir. J, 56, pp.2002049~ (2020)
- Chung, J. Y., "COVID-19 vaccines: the status and perspectives in delivery points of view", Adv. Drug Deliv. Rev, 170, pp.1~25 (2021)
- Polidoro, R. B., "Overview:Systemic inflammatory response derived from lung injury caused by SARSCoV-2 infection explains severe outcomes in COVID-19", Front Immunol, 11, pp.1626~ (2020)
- Robertson, J., "Prevalence of bone loss in a population with cystic fibrosis", Br. J. Nurs, 19, pp.636~639 (2010)
- Lehouck, A., "COPD, bone metabolism, and osteoporosis", Chest, 139, pp.648~657 (2011)
- Chauhan, V., "Bone disease in organ transplant patients : pathogenesis and management", Postgrad. Med, 124, pp.80~90 (2012)
- Graat-Verboom, L., "Risk factors for osteoporosis in Caucasian patients with moderate chronic obstructive pulmonary disease : a case control study", Bone, 50, pp.1234~1239 (2012)
- Jung, J. W., "Are asthmatic patients prone to bone loss? Ann", Allergy Asthma Immunol, 112, pp.426~431 (2014)
- DeLeon-Pennell, K. Y., "Periodontal-induced chronic inflammation triggers macrophage secretion of Ccl12 to inhibit fibroblast-mediated cardiac wound healing", JCI Insight, 2, pp.e94207~ (2017)
- Mojsilovic-Petrovic, J., "Hypoxia-inducible factor-1(HIF-1)is involved in the regulation of hypoxia-stimulated expression of monocyte chemoattractant protein-1(MCP-1", CCL2)and MCP-5(Ccl12)in astrocytes, 2007, pp.4, 12~
- Yang, J., "Diverse injury pathways induce alveolar epithelial cell CCL2", 12, which promotes lung fibrosis, 2020, pp.62, 622~632
- Popiolek-Barczyk, K., "The CCL2", CCL7, CCR2 pathway is substantially and persistently upregulated in mice after traumatic brain injury, and CCL2modulates the complement system in microglia, pp.Mol. Cell Probes, 2020[DOI]
- Longobardi, L., "TGF-beta type II receptor", MCP-5 axis : at the crossroad between joint and growth plate development, 2012, pp.23, 71~81
- Longobardi, L., "Role of the C-C chemokine receptor-2 in a murine model of injury-induced osteoarthritis", Osteoarthritis Cartilage, 25, pp.914~925 (2017)
- Kobayashi, K., "Jr IKKbeta in postnatal perichondrium remotely controls endochondral ossification of the growth plate through downregulation of MCP-5", Cell Death Differ, 22, pp.852~861 (2015)
- Jiang, Z., "Lack of SOCS3 increases LPS-induced murine acute lung injury through modulation of Ly6C(+)macrophages", Respir. Res, 18, pp.217~ (2017)
- Poole, J. A., "Age impacts pulmonary inflammation and systemic bone response to inhaled organic dust exposure", J. Toxicol. Environ. Health A, 78, pp.1201~1216 (2015)
- Poole, J. A., "Intranasal organic dust exposure-induced airway adaptation response marked by persistent lung inflammation and pathology in mice", Am. J. Physiol. Lung Cell Mol. Physiol, 296, pp.L1085~L1095 (2009)
- Ma, C., "HDAC6 inactivates Runx2 promoter to block osteogenesis of bone marrow stromal cells in age-related bone loss of mice", Stem Cell Res. Ther, 12, pp.484~ (2021)
- Bouxsein, M. L., "Guidelines for assessment of bone microstructure in rodents using micro-computed tomography", J. Bone Miner. Res, 25, pp.1468~1486 (2010)
- Dempster, D. W., "Standardized nomenclature, symbols, and units for bone histomorphometry : a 2012 update of the report of the ASBMR Histomorphometry Nomenclature Committee", J. Bone Miner. Res, 28, pp.2~17 (2013)
- Wang, Y. G., "AMPK promotes osteogenesis and inhibits adipogenesis through AMPK-Gfi1-OPN axis", Cell Signal, 28, pp.1270~1282 (2016)
- Broxmeyer, H. E., "Chemokines in hematopoiesis", Curr. Opin. Hematol, 15, pp.49~58 (2008)
- Boyle, W. J., "Osteoclast differentiation and activation", Nature, 423, pp.337~342 (2003)
- Intemann, J., "Importance of osteocyte-mediated regulation of bone remodelling in inflammatory bone disease", Swiss Med. Wkly, 150, pp.w20187~ (2020)
- Li, B. H., "Chemokines and their receptors promoting the recruitment of myeloid-derived suppressor cells into the tumor", Mol. Immunol, 117, pp.201~215 (2020)
- Hui, J., "Loss of Nucleobindin-2", Nesfatin-1increases lipopolysaccharide-induced murine acute lung inflammation, 2021, pp.385, 87~103
- Wang, W., "Macrophage micro-RNA-155 promotes lipopolysaccharideinduced acute lung injury in mice and rats", Am. J. Physiol. Lung Cell Mol. Physiol, 311, pp.L494~L506 (2016)
- Dusad, A., "Organic dust, lipopolysaccharide, and peptidoglycan inhalant exposures result in bone loss", disease, 2013, pp.49, 829~836
- Nelson, A. J., "Sex differences impact the lung-bone inflammatory response to repetitive inhalant lipopolysaccharide exposures in mice", J. Immunotoxicol, 15, pp.73~81 (2018)
- Poole, J. A., "Toll-like receptor 2 regulates organic dust-induced airway inflammation", Am. J. Respir. Cell Mol. Biol, 45, pp.711~719 (2011)
- Walsh, N. C., "Rheumatic diseases : the effects of inflammation on bone", Immunol. Rev, 208, pp.228~251 (2005)
- Nair, S. P., "Bacterially induced bone destruction : mechanisms and misconceptions", Infect. Immun, 64, pp.2371~2380 (1996)
- Kishimoto, T., "Peptidoglycan and lipopolysaccharide synergistically enhance bone resorption and osteoclastogenesis", J. Periodontal. Res, 47, pp.446~454 (2012)
- Takami, M., "Stimulation by toll-like receptors inhibits osteoclast differentiation", J. Immunol, 169, pp.1516~1523 (2002)
- Lacey, D. L., "Bench to bedside : elucidation of the OPG-RANK-RANKL pathway and the development of denosumab", Nat. Rev. Drug Discov, 11, pp.401~419 (2012)
- Kearns, A. E., "Receptor activator of nuclear factor kappaB ligand and osteoprotegerin regulation of bone remodeling in health and disease", Endocr. Rev, 29, pp.155~192 (2008)
- Gan, K., "Iguratimod (T-614) suppresses RANKL-induced osteoclast differentiation and migration in RAW264.7 cells via NF-kappaB and MAPK pathways", Int. Immunopharmacol, 35, pp.294~300 (2016)
- Yang, G., "Systemic treatment with resveratrol alleviates adjuvant arthritisinterstitial lung disease in rats via modulation of JAK", STAT, Pulm. Pharmacol. Ther, pp.2019, 56[DOI]
- Sundaram, K., "FGF-2 stimulation of RANK ligand expression in Paget’s disease of bone", Mol. Endocrinol, 23, pp.1445~1454 (2009)
- Kim, S., "Transcriptional control of receptor activator of nuclear factor-kappaB ligand by the protein kinase A activator forskolin and the transmembrane glycoprotein 130-activating cytokine, oncostatin M, is exerted through multiple distal enhancers", Mol. Endocrinol, 21, pp.197~214 (2007)
- O’Brien, C. A., "STAT3 activation in stromal", osteoblastic cells is required for induction of the receptor activator of NF-kappaB ligand and stimulation of osteoclastogenesis by gp130-utilizing cytokines or interleukin-1 but not 1, 25-dihydroxyvitamin D3 or parathyroid hormone, 1999, pp.274, 19301~19308
- Srivastava, S., "Receptor activator of NF-kappaB ligand induction via Jak2 and Stat5a in mammary epithelial cells", J Biol. Chem, 278, pp.46171~46178 (2003)
- Sundaram, K., "STAT-6 mediates TRAIL induced RANK ligand expression in stromal", preosteoblast cells, 2015, pp.71, 137~144