{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T17:14:05Z","timestamp":1783098845541,"version":"3.54.6"},"reference-count":74,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,6,8]],"date-time":"2022-06-08T00:00:00Z","timestamp":1654646400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Natural Sciences and Engineering Research Council (NSERC) of Canada","award":["CRDPJ 532150-18"],"award-info":[{"award-number":["CRDPJ 532150-18"]}]},{"name":"Egg Farmers of Canada","award":["CRDPJ 532150-18"],"award-info":[{"award-number":["CRDPJ 532150-18"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Multiple strategies including the use of bioactive peptides and other nutraceuticals are being adopted to maintain bone health. This study provides an improved and deeper understanding of the pharmacological effects that a bioactive peptide IRW (Ile-Arg-Trp) extends on bone health. Our results showed that IRW treatment protects osteoblasts against Ang II induced decline in cell proliferation and restores protein levels of collagen type I alpha 2 chain (COL1A2) and alkaline phosphatase (ALP) levels in MC3T3-E1 cells (p &lt; 0.05). Apart from augmentation of these mineralization factors, the angiotensin II (Ang II) induced apoptotic stress in osteoblasts was mitigated by IRW as well. At the molecular level, IRW abolished the cytochrome-c release via modulation of pro-and anti-apoptotic genes in MC3T3-E1 cells (p &lt; 0.05). Interestingly, IRW also increased cellular levels of cytoprotective local RAAS factors such as MasR, Ang (1\u20137), ACE2, and AT2R, and lowered the levels of Ang II effector receptor (AT1R). Further, our results indicated a lower content of inflammation and osteoclastogenesis biomarkers such as cyclooxygenase 2 (COX2), nuclear factor kappa B (NF-\u03baB), and receptor activator of nuclear factor kappa-B ligand (RANKL) following IRW treatment in MC3T3-E1 cells (p &lt; 0.05). The use of an antagonist-guided cell study indicated that IRW contributed to the process of cytoprotection and proliferation of osteoblasts via Runt-related transcription factor 2 (RUNX2) in face of Ang II stress in an AT2R dependent manner. The key findings of our study showed that IRW could potentially have a therapeutic role in the treatment and\/or prevention of bone disorders.<\/jats:p>","DOI":"10.3390\/molecules27123684","type":"journal-article","created":{"date-parts":[[2022,6,12]],"date-time":"2022-06-12T22:37:20Z","timestamp":1655073440000},"page":"3684","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Tripeptide IRW Protects MC3T3-E1 Cells against Ang II Stress in an AT2R Dependent Manner"],"prefix":"10.3390","volume":"27","author":[{"given":"Nan","family":"Shang","sequence":"first","affiliation":[{"name":"Department of Agricultural Food and Nutritional Science, University of Alberta, Edmonton, AB T6G 2R3, Canada"},{"name":"College of Engineering, China Agricultural University, Beijing 100083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khushwant S.","family":"Bhullar","sequence":"additional","affiliation":[{"name":"Department of Agricultural Food and Nutritional Science, University of Alberta, Edmonton, AB T6G 2R3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianping","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Agricultural Food and Nutritional Science, University of Alberta, Edmonton, AB T6G 2R3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Morgan, E.F., and Gerstenfeld, L.C. (2021). The bone organ system: Form and function. Marcus and Feldman\u2019s Osteoporosis, Elsevier.","DOI":"10.1016\/B978-0-12-813073-5.00002-2"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1007\/s12018-015-9182-0","article-title":"Relationship Between Aldosterone and Parathyroid Hormone, and the Effect of Angiotensin and Aldosterone Inhibition on Bone Health","volume":"13","author":"Bislev","year":"2015","journal-title":"Clin. Rev. Bone Miner. Metab."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"H\u00f6gberg, U., Andersson, J., H\u00f6gberg, G., and Thiblin, I. (2018). Metabolic bone disease risk factors strongly contributing to long bone and rib fractures during early infancy: A population register study. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0208033"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1007\/s00774-020-01132-y","article-title":"Role of the renin\u2013angiotensin\u2013aldosterone system in bone metabolism","volume":"38","author":"Mo","year":"2020","journal-title":"J. Bone Miner. Metab."},{"key":"ref_5","unstructured":"Fountain, J.H., and Lappin, S.L. (2017). Physiology, Renin Angiotensin System, StatPearls Publishing."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1016\/S1357-2725(02)00306-0","article-title":"The brain renin\u2013angiotensin system: Location and physiological roles","volume":"35","author":"McKinley","year":"2003","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1177\/1470320314549791","article-title":"Expression of classical components of the renin-angiotensin system in the human eye","volume":"16","author":"White","year":"2015","journal-title":"J. Renin-Angiotensin-Aldosterone Syst."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"115041","DOI":"10.1016\/j.bone.2019.115041","article-title":"The angiotensin converting enzyme 2\/angiotensin-(1-7)\/Mas Receptor axis as a key player in alveolar bone remodeling","volume":"128","author":"Santos","year":"2019","journal-title":"Bone"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2465","DOI":"10.1096\/fj.07-098954","article-title":"Angiotensin II accelerates osteoporosis by activating osteoclasts","volume":"22","author":"Shimizu","year":"2008","journal-title":"FASEB J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2959","DOI":"10.1002\/jbmr.501","article-title":"Physiological function of the angiotensin AT1a receptor in bone remodeling","volume":"26","author":"Kaneko","year":"2011","journal-title":"J. Bone Miner. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1002\/JPER.17-0753","article-title":"Inhibition of angiotensin II receptor I prevents inflammation and bone loss in periodontitis","volume":"90","author":"Li","year":"2019","journal-title":"J. Periodontol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.atherosclerosis.2018.07.019","article-title":"Effect of irradiation and bone marrow transplantation on angiotensin II-induced aortic inflammation in ApoE knockout mice","volume":"276","author":"Patel","year":"2018","journal-title":"Atherosclerosis"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"628","DOI":"10.5114\/aoms.2015.52369","article-title":"Angiotensin II suppresses osteoblastic differentiation and mineralized nodule formation via AT1 receptor in ROS17\/2.8 cells","volume":"11","author":"Nakai","year":"2015","journal-title":"Arch. Med. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1271\/bbb.120123","article-title":"Involvement of the Skeletal Renin-Angiotensin System in Age-Related Osteoporosis of Ageing Mice","volume":"76","author":"Gu","year":"2012","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/j.archoralbio.2014.02.015","article-title":"Angiotensin II induces mitochondrial dysfunction and promotes apoptosis via JNK signalling pathway in primary mouse calvaria osteoblast","volume":"59","author":"Li","year":"2014","journal-title":"Arch. Oral Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1161\/ATVBAHA.110.216044","article-title":"Pivotal Role of Protein Kinase C\u03b4 in Angiotensin II\u2013Induced Endothelial Cyclooxygenase-2 Expression: A Link to Vascular Inflammation","volume":"31","author":"Wong","year":"2011","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1672","DOI":"10.1111\/j.1476-5381.2010.00651.x","article-title":"Inhibition of angiotensin-converting enzyme stimulates fracture healing and periosteal callus formation\u2013Role of a local renin-angiotensin system","volume":"159","author":"Garcia","year":"2010","journal-title":"Br. J. Pharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1097\/HJH.0b013e32834f6b43","article-title":"Aliskiren penetrates adipose and skeletal muscle tissue and reduces renin\u2013angiotensin system activity in obese hypertensive patients","volume":"30","author":"Boschmann","year":"2012","journal-title":"J. Hypertens."},{"key":"ref_19","first-page":"692","article-title":"Evolution of the bone mass of hypertense menopausal women in treatment with fosinopril","volume":"127","author":"Monzo","year":"2006","journal-title":"Med. Clin."},{"key":"ref_20","first-page":"57","article-title":"ARB users exhibit a lower fracture incidence than ACE inhibitor users among older hypertensive men","volume":"46","author":"Kwok","year":"2017","journal-title":"Age Ageing"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/j.nut.2013.11.005","article-title":"Shark protein improves bone mineral density in ovariectomized rats and inhibits osteoclast differentiation","volume":"30","author":"Uehara","year":"2014","journal-title":"Nutrition"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e12529","DOI":"10.1111\/jfbc.12529","article-title":"Bone health-promoting bioactive peptides","volume":"43","author":"Ahn","year":"2019","journal-title":"J. Food Biochem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3585","DOI":"10.1021\/acs.jafc.1c06289","article-title":"Bioactive Peptides: From Basic Research to Clinical Trials and Commercialization","volume":"70","author":"Duffuler","year":"2022","journal-title":"J. Agric. Food Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1016\/j.foodchem.2010.07.004","article-title":"Antioxidant and antimicrobial peptidic hydrolysates from muscle protein sources and by-products","volume":"124","author":"Harnedy","year":"2011","journal-title":"Food Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"14402","DOI":"10.1021\/acs.jafc.0c05544","article-title":"A Novel Angiotensin Converting Enzyme 2 (ACE2) Activating Peptide: A Reflection of 10 Years of Research on a Small Peptide Ile-Arg-Trp (IRW)","volume":"68","author":"Wu","year":"2020","journal-title":"J. Agric. Food Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2120","DOI":"10.1021\/jf3046076","article-title":"Structure and Activity Study of Egg Protein Ovotransferrin Derived Peptides (IRW and IQW) on Endothelial Inflammatory Response and Oxidative Stress","volume":"61","author":"Majumder","year":"2013","journal-title":"J. Agric. Food Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"11330","DOI":"10.1021\/acs.jafc.8b03501","article-title":"Egg White-Derived Tripeptide IRW (Ile-Arg-Trp) Is an Activator of Angiotensin Converting Enzyme 2","volume":"66","author":"Liao","year":"2018","journal-title":"J. Agric. Food Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1016\/j.bbagen.2019.04.007","article-title":"Tripeptide IRW initiates differentiation in osteoblasts via the RUNX2 pathway","volume":"1863","author":"Shang","year":"2019","journal-title":"Biochim. Biophys. Acta (BBA)-Gen. Subj."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1021\/acs.jafc.0c07831","article-title":"Tripeptide IRW Upregulates NAMPT Protein Levels in Cells and Obese C57BL\/6J Mice","volume":"69","author":"Bhullar","year":"2021","journal-title":"J. Agric. Food Chem."},{"key":"ref_30","first-page":"669","article-title":"Mitochondrial division inhibitor Mdivi-1 ameliorates angiotensin II-induced endothelial dysfunction","volume":"68","author":"Chen","year":"2016","journal-title":"Sheng Li Xue Bao Acta Physiol. Sin."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1161\/CIRCRESAHA.116.307708","article-title":"Role of the ACE2\/angiotensin 1\u20137 axis of the renin\u2013angiotensin system in heart failure","volume":"118","author":"Patel","year":"2016","journal-title":"Circ. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4608165","DOI":"10.1155\/2019\/4608165","article-title":"AT1R-Mediated Apoptosis of Bone Marrow Mesenchymal Stem Cells Is Associated with mtROS Production and mtDNA Reduction","volume":"2019","author":"Zhang","year":"2019","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"511799","DOI":"10.3389\/fphys.2020.511799","article-title":"The Effect of Inflammation on Bone","volume":"11","author":"Epsley","year":"2021","journal-title":"Front. Physiol."},{"key":"ref_34","first-page":"105","article-title":"The epidemiology of osteoporosis","volume":"133","author":"Clynes","year":"2020","journal-title":"Br. Med. Bull."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1007\/s00198-020-05554-2","article-title":"A scorecard for osteoporosis in Canada and seven Canadian provinces","volume":"32","author":"Kendler","year":"2021","journal-title":"Osteoporos. Int."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1161\/01.CIR.0000155621.10213.06","article-title":"Hyperparathyroidism and the Calcium Paradox of Aldosteronism","volume":"111","author":"Chhokar","year":"2005","journal-title":"Circulation"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1007\/s00198-015-3348-y","article-title":"Renin inhibitor aliskiren exerts beneficial effect on trabecular bone by regulating skeletal renin-angiotensin system and kallikrein-kinin system in ovariectomized mice","volume":"27","author":"Zhang","year":"2016","journal-title":"Osteoporos. Int."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1007\/s00198-014-2992-y","article-title":"Local renin-angiotensin system is associated with bone mineral density of glucocorticoid-induced osteoporosis patients","volume":"26","author":"Shuai","year":"2015","journal-title":"Osteoporos. Int."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1093\/jn\/126.1.86","article-title":"Dietary Casein Phosphopeptides Prevent Bone Loss in Aged Ovariectomized Rats","volume":"126","author":"Tsuchita","year":"1996","journal-title":"J. Nutr."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1016\/j.bone.2009.10.035","article-title":"Hydrolyzed collagen improves bone metabolism and biomechanical parameters in ovariectomized mice: An in vitro and in vivo study","volume":"46","author":"Guillerminet","year":"2010","journal-title":"Bone"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1909","DOI":"10.1007\/s00198-011-1788-6","article-title":"Hydrolyzed collagen improves bone status and prevents bone loss in ovariectomized C3H\/HeN mice","volume":"23","author":"Guillerminet","year":"2012","journal-title":"Osteoporos. Int."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1016\/j.bbrc.2014.09.121","article-title":"Collagen-derived dipeptide prolyl-hydroxyproline promotes differentiation of MC3T3-E1 osteoblastic cells","volume":"453","author":"Kimira","year":"2014","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"103697","DOI":"10.1016\/j.jff.2019.103697","article-title":"Porcine bone collagen peptides promote osteoblast proliferation and differentiation by activating the PI3K\/Akt signaling pathway","volume":"64","author":"Zhu","year":"2020","journal-title":"J. Funct. Foods"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1017\/S0007114507744434","article-title":"Effects of bioactive peptides isoleucine-proline-proline (IPP), valine-proline-proline (VPP) and leucine-lysine-proline (LKP) on gene expression of osteoblasts differentiated from human mesenchymal stem cells","volume":"98","author":"Huttunen","year":"2007","journal-title":"Br. J. Nutr."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1016\/j.jnutbio.2007.09.006","article-title":"Long-term effects of tripeptide Ile-Pro-Pro on osteoblast differentiation in vitro","volume":"19","author":"Huttunen","year":"2008","journal-title":"J. Nutr. Biochem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1002\/cbf.3325","article-title":"Fish bone peptide promotes osteogenic differentiation of MC3T3-E1 pre-osteoblasts through upregulation of MAPKs and Smad pathways activated BMP-2 receptor","volume":"36","author":"Heo","year":"2018","journal-title":"Cell Biochem. Funct."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1016\/j.procbio.2013.06.031","article-title":"Tetrameric peptide purified from hydrolysates of biodiesel byproducts of Nannochloropsis oculata induces osteoblastic differentiation through MAPK and Smad pathway on MG-63 and D1 cells","volume":"48","author":"Nguyen","year":"2013","journal-title":"Process Biochem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.jnutbio.2016.08.003","article-title":"Akt drives buffalo casein-derived novel peptide-mediated osteoblast differentiation","volume":"38","author":"Reddi","year":"2016","journal-title":"J. Nutr. Biochem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.nut.2017.06.010","article-title":"Antioxidative peptide from milk exhibits antiosteopenic effects through inhibition of oxidative damage and bone-resorbing cytokines in ovariectomized rats","volume":"43\u201344","author":"Mada","year":"2017","journal-title":"Nutrition"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/S1570-9639(03)00235-8","article-title":"Activation of osteo-progenitor cells by a novel synthetic peptide derived from the bone morphogenetic protein-2 knuckle epitope","volume":"1651","author":"Saito","year":"2003","journal-title":"Biochim. Biophys. Acta (BBA)-Proteins Proteom."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"7057","DOI":"10.1016\/j.biomaterials.2012.06.036","article-title":"Osteogenesis induced by a bone forming peptide from the prodomain region of BMP-7","volume":"33","author":"Kim","year":"2012","journal-title":"Biomaterials"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e328","DOI":"10.1038\/emm.2017.40","article-title":"Bone-forming peptide-2 derived from BMP-7 enhances osteoblast differentiation from multipotent bone marrow stromal cells and bone formation","volume":"49","author":"Kim","year":"2017","journal-title":"Exp. Mol. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1056\/NEJMoa0809493","article-title":"Denosumab for Prevention of Fractures in Postmenopausal Women with Osteoporosis","volume":"361","author":"Cummings","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/S0140-6736(17)32137-2","article-title":"Effects of teriparatide and risedronate on new fractures in post-menopausal women with severe osteoporosis (VERO): A multicentre, double-blind, double-dummy, randomised controlled trial","volume":"391","author":"Kendler","year":"2018","journal-title":"Lancet"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1704","DOI":"10.1172\/JCI20427","article-title":"A crucial role of caspase-3 in osteogenic differentiation of bone marrow stromal stem cells","volume":"114","author":"Miura","year":"2004","journal-title":"J. Clin. Investig."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1002\/cbin.11137","article-title":"Cell death: A review of the major forms of apoptosis, necrosis and autophagy","volume":"43","year":"2019","journal-title":"Cell Biol. Int."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.bbrc.2005.05.092","article-title":"Death receptors, Fas and TRAIL receptors, are involved in human osteoclast apoptosis","volume":"333","author":"Roux","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1136\/mp.50.3.132","article-title":"Apoptosis in bone physiology and disease","volume":"50","author":"Hughes","year":"1997","journal-title":"Mol. Pathol."},{"key":"ref_59","first-page":"2","article-title":"Using Bcl-xL anti-apoptotic protein for altering target cell apoptosis","volume":"15","author":"Iz","year":"2012","journal-title":"Electron. J. Biotechnol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1016\/j.bone.2006.02.062","article-title":"Hydrogen peroxide-induced oxidative stress in MC3T3-E1 cells: The effects of glutamate and protection by purines","volume":"39","author":"Fatokun","year":"2006","journal-title":"Bone"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s13018-015-0152-5","article-title":"Role of apoptosis in pathogenesis and treatment of bone-related diseases","volume":"10","author":"Mollazadeh","year":"2015","journal-title":"J. Orthop. Surg. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1712","DOI":"10.1359\/jbmr.080617","article-title":"Connexin 43 Is Required for the Anti-Apoptotic Effect of Bisphosphonates on Osteocytes and Osteoblasts In Vivo","volume":"23","author":"Plotkin","year":"2008","journal-title":"J. Bone Miner. Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.bone.2010.08.008","article-title":"Novel actions of bisphosphonates in bone: Preservation of osteoblast and osteocyte viability","volume":"49","author":"Bellido","year":"2011","journal-title":"Bone"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"325","DOI":"10.2174\/1568010054022015","article-title":"Osteoblasts and Osteoclasts in Bone Remodeling and Inflammation","volume":"4","author":"Tanaka","year":"2005","journal-title":"Curr. Drug Targets-Inflamm. Allergy"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/S0169-328X(96)00240-9","article-title":"Dexamethasone attenuates NF-\u03ba B DNA binding activity without inducing I \u03ba B levels in rat brain in vivo","volume":"45","author":"Unlap","year":"1997","journal-title":"Mol. Brain Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1111\/j.1432-1033.1997.00063.x","article-title":"1\u03b1,25-Dihydroxyvitamin D3 and a Variety of its Natural Metabolites Transcriptionally Repress Nuclear-Factor-\u03baB-Mediated Interleukin-8 Gene Expression","volume":"250","author":"Harant","year":"1997","journal-title":"Eur. J. Biochem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"5940","DOI":"10.4049\/jimmunol.172.10.5940","article-title":"Curcumin (diferuloylmethane) inhibits receptor activator of NF-\u03baB ligand-induced NF-\u03baB activation in osteoclast precursors and suppresses osteoclastogenesis","volume":"172","author":"Bharti","year":"2004","journal-title":"J. Immunol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"492","DOI":"10.2174\/1381612826666200115092015","article-title":"Emerging Role of Angiotensin AT2 Receptor in Anti-Inflammation: An Update","volume":"26","author":"Patel","year":"2020","journal-title":"Curr. Pharm. Des."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1975","DOI":"10.1111\/jcmm.12574","article-title":"The CD4+ AT2R+ T cell subpopulation improves post-infarction remodelling and restores cardiac function","volume":"19","author":"Skorska","year":"2015","journal-title":"J. Cell. Mol. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"BSR20190429","DOI":"10.1042\/BSR20190429","article-title":"Prevention of lipopolysaccharide-induced CD11b+ immune cell infiltration in the kidney: Role of AT2 receptors","volume":"39","author":"Patel","year":"2019","journal-title":"Biosci. Rep."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1161\/HYPERTENSIONAHA.109.147843","article-title":"Direct Angiotensin II Type 2 Receptor Stimulation Acts Anti-Inflammatory through Epoxyeicosatrienoic Acid and Inhibition of Nuclear Factor \u03baB","volume":"55","author":"Rompe","year":"2010","journal-title":"Hypertension"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"5995","DOI":"10.1021\/jm049715t","article-title":"Design, synthesis, and biological evaluation of the first selective nonpeptide AT2 receptor agonist","volume":"47","author":"Wan","year":"2004","journal-title":"J. Med. Chem."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1550","DOI":"10.1159\/000479272","article-title":"Angiotensin II regulates dendritic cells through activation of NF-\u03baB\/p65, ERK1\/2 and STAT1 pathways","volume":"42","author":"Meng","year":"2017","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1139\/y11-108","article-title":"The regenerative potential of angiotensin AT2 receptor in cardiac repair","volume":"90","author":"Ludwig","year":"2012","journal-title":"Can. J. Physiol. 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