{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T22:10:47Z","timestamp":1792188647663,"version":"4.4.0"},"reference-count":50,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2017,8,8]],"date-time":"2017-08-08T00:00:00Z","timestamp":1502150400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000980","name":"Arthritis Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000980","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007253","name":"Nancy Taylor Foundation for Chronic Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007253","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AR48182"],"award-info":[{"award-number":["AR48182"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AR50245"],"award-info":[{"award-number":["AR50245"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AG15768"],"award-info":[{"award-number":["AG15768"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AR48852"],"award-info":[{"award-number":["AR48852"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AG46927"],"award-info":[{"award-number":["AG46927"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["OD10707"],"award-info":[{"award-number":["OD10707"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To investigate whether short\u2010term, systemic depletion of macrophages can mitigate osteoarthritis (OA) following injury in the setting of obesity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p><jats:italic>CSF\u20101R\u2013GFP+<\/jats:italic> macrophage Fas\u2010induced apoptosis (MaFIA)\u2013transgenic mice that allow conditional depletion of macrophages were placed on a high\u2010fat diet and underwent surgery to induce knee OA. A small molecule (AP20187) was administrated to deplete macrophages in MaFIA mice. The effects of macrophage depletion on acute joint inflammation, OA severity, and arthritic bone changes were evaluated using histology and micro\u2013computed tomography. Immunohistochemical analysis was performed to identify various immune cells. The levels of serum and synovial fluid cytokines were also measured.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Macrophage\u2010depleted mice had significantly fewer M1 and M2 macrophages in the surgically operated joints relative to controls and exhibited decreased osteophyte formation immediately following depletion. Surprisingly, macrophage depletion did not attenuate the severity of OA in obese mice; instead, it induced systemic inflammation and led to a massive infiltration of CD3+ T cells and particularly neutrophils, but not B cells, into the injured joints. Macrophage\u2010depleted mice also demonstrated a markedly increased number of proinflammatory cytokines including granulocyte colony\u2010stimulating factor, interleukin\u20101\u03b2 (IL\u20101\u03b2), IL\u20106, IL\u20108, and tumor necrosis factor in both serum and joint synovial fluid, although the mice showed a trend toward decreased levels of insulin and leptin in serum after macrophage depletion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings indicate that macrophages are vital for modulating homeostasis of immune cells in the setting of obesity and suggest that more targeted approaches of depleting specific macrophage subtypes may be necessary to mitigate inflammation and OA in the setting of obesity.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.40161","type":"journal-article","created":{"date-parts":[[2017,5,23]],"date-time":"2017-05-23T21:11:43Z","timestamp":1495573903000},"page":"1772-1783","source":"Crossref","is-referenced-by-count":129,"title":["Conditional Macrophage Depletion Increases Inflammation and Does Not Inhibit the Development of Osteoarthritis in Obese Macrophage Fas\u2010Induced Apoptosis\u2013Transgenic Mice"],"prefix":"10.1002","volume":"69","author":[{"given":"Chia\u2010Lung","family":"Wu","sequence":"first","affiliation":[{"name":"Washington University and Shriners Hospitals for Children St. Louis Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenna","family":"McNeill","sequence":"additional","affiliation":[{"name":"Washington University and Shriners Hospitals for Children St. Louis Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelsey","family":"Goon","sequence":"additional","affiliation":[{"name":"Washington University and Shriners Hospitals for Children St. Louis Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dianne","family":"Little","sequence":"additional","affiliation":[{"name":"Purdue University West Lafayette Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"Kimmerling","sequence":"additional","affiliation":[{"name":"Washington University and Shriners Hospitals for Children St. Louis Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet","family":"Huebner","sequence":"additional","affiliation":[{"name":"Duke University Medical Center Durham North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia","family":"Kraus","sequence":"additional","affiliation":[{"name":"Duke University Medical Center Durham North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farshid","family":"Guilak","sequence":"additional","affiliation":[{"name":"Washington University and Shriners Hospitals for Children St. Louis Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,8,8]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.100263"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2009-0925"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12034"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M706762200"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000251608.09329.9a"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI29881"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0210072"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0024358"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2014.05.013"},{"key":"e_1_2_7_11_1","doi-asserted-by":"crossref","first-page":"lb656","DOI":"10.1096\/fasebj.30.1_supplement.lb656","article-title":"Chondrocyte metabolic flexibility and early\u2010stage osteoarthritis in mice fed a high\u2010fat diet","volume":"30","author":"Donovan E","year":"2016","journal-title":"FASEB J"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2014-205601"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.37796"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.33423"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar2099"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.22337"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2004.03.003"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0903442"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2007.03.006"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2010.03.014"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4899-7606-2_5"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.34533"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2006.11.006"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0054633"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2014.46"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.23103"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr.22952"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39486"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39842"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jss.2005.08.026"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.2.1232"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/icb.2016.74"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-01-265959"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0099575"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2014.80"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-03-453217"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2014.04.027"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kev270"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2016.07.020"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201242526"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.11.003"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.03.024"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/emm.2013.89"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.2.922"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.06.014"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-394299-9.00001-1"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI42845"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2008.08.015"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0810472"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-07-445189"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI57990"}],"container-title":["Arthritis &amp; Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.40161","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.40161","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T16:26:18Z","timestamp":1759940778000},"score":1,"resource":{"primary":{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/10.1002\/art.40161"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,8,8]]},"references-count":50,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2017,9]]}},"alternative-id":["10.1002\/art.40161"],"URL":"https:\/\/doi.org\/10.1002\/art.40161","archive":["Portico"],"relation":{},"ISSN":["2326-5191","2326-5205"],"issn-type":[{"value":"2326-5191","type":"print"},{"value":"2326-5205","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,8,8]]}}}