{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T04:30:35Z","timestamp":1773721835794,"version":"3.50.1"},"reference-count":105,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T00:00:00Z","timestamp":1752192000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Anim Models and Exp Med"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The subcutaneous air pouch model has been used extensively to study the pathophysiology of inflammatory conditions such as joint diseases and the potential efficacy of pharmacological treatments in\u00a0vivo. Delivery of air between the subcutaneous and dermal layer of the intra\u2010scapular zone of the rodent generates an environment analogous to the synovial joint space. Introduction of monosodium urate crystals or calcium pyrophosphate crystals into the air space produces a sterile acute inflammatory response mimicking clinical gout and pseudogout, respectively. The inflammatory response can be quantitatively and robustly evaluated by measuring leukocyte infiltration, inflammatory cytokine production, eicosanoid release, complement activation and reactive oxygen species generation. Despite the utility of this model, great variation exists within the literature regarding the design, sampling time points, and endpoints measured. This systematic review summarizes the current literature on the subcutaneous air pouch model studying monosodium urate or calcium pyrophosphate crystals and provides recommendations for standardizing and improving the reliability and validity of this model. Standardizing the experimental approach would improve inter\u2010study comparability, increase the internal validity of studies and reproducibility of results, and ultimately improve the understanding of gout and pseudogout and accelerate the discovery of new pharmacological therapies.<\/jats:p>","DOI":"10.1002\/ame2.70058","type":"journal-article","created":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T07:48:46Z","timestamp":1752220126000},"page":"1611-1627","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Systematic review of the subcutaneous air pouch model using monosodium urate and calcium pyrophosphate and recommendations for studying crystal\u2010related arthropathies"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-5747-4491","authenticated-orcid":false,"given":"Wenu","family":"Hewage","sequence":"first","affiliation":[{"name":"School of Pharmacy and Medical Science Griffith University  Gold Coast Queensland Australia"},{"name":"School of Medicine and Dentistry Griffith University  Gold Coast Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josif","family":"Vidimce","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Medical Science Griffith University  Gold Coast Queensland Australia"},{"name":"School of Medicine and Dentistry Griffith University  Gold Coast Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryan G.","family":"Shiels","sequence":"additional","affiliation":[{"name":"Queensland Alliance for Environmental Health Science University of Queensland  Brisbane Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Morgan","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Physiology University of Melbourne  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew C.","family":"Bulmer","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Medical Science Griffith University  Gold Coast Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,7,11]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keh640"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-200464210-00003"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2017.04.008"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.220425"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11926-013-0400-9"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.JAA.0000475472.40251.58"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02248"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-34570-5"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2009.00851.x"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr.24180"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04516"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.3109\/08820139.2016.1153651"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar2952"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2020.105684"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0090-1229(82)90235-5"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1923"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2017.155"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xpro.2024.102888"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01996113"},{"key":"e_1_2_12_21_1","volume-title":"Cell Culture","author":"Franco\u2010Molina MA","year":"2018"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1953.63690130001006"},{"issue":"3","key":"e_1_2_12_23_1","first-page":"271","article-title":"Evidence for hyaluronan production in the air pouch model in rats","volume":"19","author":"Generini S","year":"2001","journal-title":"Clin Exp Rheumatol"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/0471141755.ph0506s56"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.1711410406"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metop.2021.100100"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000001137"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-203803"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1097\/MJT.0b013e31829ea238"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0185704"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kex499"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0117770"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep38622"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/2193-1801-2-659"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2014-206074"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1186\/1756-0500-4-443"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.2147\/JIR.S307796"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26041071"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/1756-185X.14089"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/smll.201800703"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2021.115582"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2021.102103"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.638676"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.695712"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1071630"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1186\/s42358-023-00307-1"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2023.116147"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.21238"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.11271"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2005.11.010"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.27456"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar2222"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.9.6370"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1939-165X.2009.00166.x"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.2c19684"},{"issue":"4","key":"e_1_2_12_56_1","first-page":"361","article-title":"Does rofecoxib increase TNF\u2010alpha levels?","volume":"24","author":"Nalbant S","year":"2006","journal-title":"Clin Exp Rheumatol"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2020.105546"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.1097\/00045391-199603000-00003"},{"key":"e_1_2_12_59_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.11079"},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.47.3.241"},{"issue":"12","key":"e_1_2_12_61_1","first-page":"2674","article-title":"Inhibitory effect of low density lipoprotein on the inflammation\u2010inducing activity of calcium pyrophosphate dihydrate crystals","volume":"28","author":"Kumagai Y","year":"2001","journal-title":"J Rheumatol"},{"key":"e_1_2_12_62_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1987.tb08971.x"},{"key":"e_1_2_12_63_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780311211"},{"key":"e_1_2_12_64_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.45.8.673"},{"key":"e_1_2_12_65_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.10326"},{"issue":"5","key":"e_1_2_12_66_1","first-page":"780","article-title":"A comparison of five preparations of synthetic monosodium urate monohydrate crystals","volume":"19","author":"Fam AG","year":"1992","journal-title":"J Rheumatol"},{"key":"e_1_2_12_67_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780360912"},{"key":"e_1_2_12_68_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1203215"},{"key":"e_1_2_12_69_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2009.109355"},{"key":"e_1_2_12_70_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.10709"},{"key":"e_1_2_12_71_1","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.201400626"},{"key":"e_1_2_12_72_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep28793"},{"key":"e_1_2_12_73_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.43.3.487"},{"key":"e_1_2_12_74_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-024-03335-4"},{"key":"e_1_2_12_75_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keg305"},{"key":"e_1_2_12_76_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01199"},{"key":"e_1_2_12_77_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-018-1550-y"},{"key":"e_1_2_12_78_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01710"},{"key":"e_1_2_12_79_1","doi-asserted-by":"publisher","DOI":"10.1248\/yakushi.130.397"},{"key":"e_1_2_12_80_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-008-9078-8"},{"key":"e_1_2_12_81_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.0c00229"},{"key":"e_1_2_12_82_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780390718"},{"key":"e_1_2_12_83_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-018-1699-4"},{"key":"e_1_2_12_84_1","doi-asserted-by":"publisher","DOI":"10.1016\/0090-6980(94)90018-3"},{"key":"e_1_2_12_85_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2020.114125"},{"key":"e_1_2_12_86_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10787-020-00758-8"},{"key":"e_1_2_12_87_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(199805)41:5<900::AID-ART18>3.0.CO;2-K"},{"key":"e_1_2_12_88_1","first-page":"15","article-title":"The effect of montelukast in a model of gouty arthritis induced by sodium monourate crystals","volume":"52","author":"Ponce L","year":"2011","journal-title":"Investig Clin"},{"key":"e_1_2_12_89_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2012.07.024"},{"key":"e_1_2_12_90_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-15106-0"},{"key":"e_1_2_12_91_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1003746"},{"key":"e_1_2_12_92_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar2435"},{"key":"e_1_2_12_93_1","doi-asserted-by":"publisher","DOI":"10.7326\/M14-2070"},{"key":"e_1_2_12_94_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-19252-x"},{"key":"e_1_2_12_95_1","doi-asserted-by":"publisher","DOI":"10.1177\/03000605211055618"},{"key":"e_1_2_12_96_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21124269"},{"issue":"1","key":"e_1_2_12_97_1","first-page":"1","article-title":"The evolving landscape of gout in the female: a narrative review","volume":"2","author":"Lee J","year":"2024","journal-title":"Gout Urate Cryst Deposition Dis"},{"key":"e_1_2_12_98_1","doi-asserted-by":"publisher","DOI":"10.2147\/JIR.S178288"},{"key":"e_1_2_12_99_1","doi-asserted-by":"publisher","DOI":"10.21769\/BioProtoc.2754"},{"key":"e_1_2_12_100_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-015-0550-4"},{"key":"e_1_2_12_101_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.40650"},{"key":"e_1_2_12_102_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2017.04.031"},{"key":"e_1_2_12_103_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2016.00213"},{"key":"e_1_2_12_104_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpz1.183"},{"key":"e_1_2_12_105_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2007.173"},{"key":"e_1_2_12_106_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201545520"}],"container-title":["Animal Models and Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ame2.70058","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T00:51:51Z","timestamp":1766019111000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ame2.70058"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,11]]},"references-count":105,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["10.1002\/ame2.70058"],"URL":"https:\/\/doi.org\/10.1002\/ame2.70058","archive":["Portico"],"relation":{},"ISSN":["2576-2095","2576-2095"],"issn-type":[{"value":"2576-2095","type":"print"},{"value":"2576-2095","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,11]]},"assertion":[{"value":"2024-06-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}