{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:29:50Z","timestamp":1785716990993,"version":"3.56.0"},"reference-count":63,"publisher":"Wiley","issue":"24","license":[{"start":{"date-parts":[[2024,12,25]],"date-time":"2024-12-25T00:00:00Z","timestamp":1735084800000},"content-version":"vor","delay-in-days":24,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AR069620"],"award-info":[{"award-number":["AR069620"]}],"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":["CA093900"],"award-info":[{"award-number":["CA093900"]}],"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":["DE022327"],"award-info":[{"award-number":["DE022327"]}],"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":["DE030697"],"award-info":[{"award-number":["DE030697"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Macrophage efferocytosis (clearance of apoptotic cells) is crucial for tissue homeostasis and wound repair, where macrophages secrete factors that promote resolution of inflammation and regenerative signalling. This study examined the role of efferocytic macrophage\u2010associated CCL2 secretion, its influence on mesenchymal stem\/progenitor cell (MSPC) chemotaxis, and in\u00a0vivo cell recruitment using <jats:italic>Ccr2<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> (KO) mice with disrupted CCL2 receptor signalling in two regenerative models: ossicle implants and ulnar stress fractures. Single cell RNA sequencing and PCR validation indicated that efferocytosis of various apoptotic cells at bone injury sites (osteoblasts, pre\u2010osteoblasts, MSPC) upregulated CCL2. CCL2 gradients enhanced MSPC migration through type I collagen matrices. In\u00a0vivo, MSPC (LepR<jats:sup>+<\/jats:sup>) infiltration was significantly reduced while macrophage (F4\/80<jats:sup>+<\/jats:sup>) infiltration increased in KO ossicle implants versus WT. In ulnar stress fractures, micro\u2010CT revealed increased mineralized callus incidence in CCR2 KO male mice 5\u2009days post injury (dpi) versus WT. By 7\u2010dpi callus fractional bone volume, trabecular thickness, and bone mineral density were increased versus WT. Immunohistochemistry of mice 5\u2010dpi confirmed an increase in callus area (including soft tissue); however, the percent of osteoprogenitors (%Osx<jats:sup>+<\/jats:sup>) within the callus was not different. These findings suggest that CCL2 differentially impacts MSPC recruitment depending on bone wound healing model.<\/jats:p>","DOI":"10.1111\/jcmm.70300","type":"journal-article","created":{"date-parts":[[2024,12,25]],"date-time":"2024-12-25T16:39:38Z","timestamp":1735144778000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["<scp>CCL2<\/scp>\/<scp>CCR2<\/scp> Signalling in Mesenchymal Stem\/Progenitor Cell Recruitment and Fracture Healing in Mice"],"prefix":"10.1111","volume":"28","author":[{"given":"Rahasudha","family":"Kannan","sequence":"first","affiliation":[{"name":"Department of Periodontics and Oral Medicine University of Michigan School of Dentistry  Ann Arbor Michigan USA"},{"name":"Department of Biomedical Engineering University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy J.","family":"Koh","sequence":"additional","affiliation":[{"name":"Department of Periodontics and Oral Medicine University of Michigan School of Dentistry  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"Robert N.","family":"Kent","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaira","family":"Bhutada","sequence":"additional","affiliation":[{"name":"Department of Periodontics and Oral Medicine University of Michigan School of Dentistry  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatima","family":"Wasi","sequence":"additional","affiliation":[{"name":"Department of Periodontics and Oral Medicine University of Michigan School of Dentistry  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leon","family":"Wagner","sequence":"additional","affiliation":[{"name":"Department of Periodontics and Oral Medicine University of Michigan School of Dentistry  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Kozloff","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendon M.","family":"Baker","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2896-1455","authenticated-orcid":false,"given":"Hernan","family":"Roca","sequence":"additional","affiliation":[{"name":"Department of Periodontics and Oral Medicine University of Michigan School of Dentistry  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9173-9123","authenticated-orcid":false,"given":"Laurie K.","family":"McCauley","sequence":"additional","affiliation":[{"name":"Department of Periodontics and Oral Medicine University of Michigan School of Dentistry  Ann Arbor Michigan USA"},{"name":"Department of Pathology University of Michigan Medical School  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,25]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2015.10.019"},{"key":"e_1_2_9_3_1","first-page":"1","article-title":"Prix Fixe: Efferocytosis as a Four\u2010Course Meal","volume":"403","author":"Martinez J.","year":"2017","journal-title":"Current Topics in Microbiology and Immunology"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580\u2010020\u20100232\u20101"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1315153111"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.3196"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-018-0249-1"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/JLB.5HI0420-648R"},{"issue":"3","key":"e_1_2_9_9_1","first-page":"214","article-title":"Enhanced Efferocytosis of Apoptotic Cardiomyocytes Through MER Tyrosine Kinase Links Acute Inflammation Resolution to Cardiac Repair After Infarction","volume":"162","author":"Wan E.","year":"2009","journal-title":"Psychiatry: Interpersonal and Biological Processes"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1502270"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1821601116"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.354"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2422"},{"issue":"1","key":"e_1_2_9_14_1","first-page":"1","article-title":"Modulation of Macrophage Activity During Fracture Repair Has Differential Effects in Young Adult and Elderly Mice","volume":"28","author":"Shantz J. A. S.","year":"2014","journal-title":"Journal of Orthopaedic Trauma"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.13056"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2017.02.017"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2008.08.128"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1601520"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.25567"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.631714"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2018.12.004"},{"issue":"2759","key":"e_1_2_9_22_1","first-page":"1","article-title":"More Than Just Attractive: How CCL2 Influences Myeloid Cell Behavior Beyond Chemotaxis","volume":"10","author":"Gschwandtner M.","year":"2019","journal-title":"Frontiers in Immunology"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0104954"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035036"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/exd.12701"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.003186"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201404487"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01804"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11914-017-0384-x"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.22.12053"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2016.11.008"},{"key":"e_1_2_9_32_1","first-page":"1153","volume-title":"Functional Angiogenesis Requires Microenvironmental Cues Balancing Endothelial Cell Migration and Proliferation","author":"Wang W. Y.","year":"2020"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-59745-104-8_7"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00300234"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S8756-3282(03)00199-6"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2010.02.030"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.141"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2019"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.24170"},{"key":"e_1_2_9_40_1","volume-title":"StatPearls","author":"Sheen J. R.","year":"2021"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-472X(02)00829-9"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.05318-11"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/cpr.13115"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119798"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.111.005074"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1359-6101(99)00005-2"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mbplus.2019.03.002"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0022818"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0b013e31827802b5"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-013-9718-6"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-014-9914-z"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1945"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1352819"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.240"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.0070614"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1097\/BOT.0000000000000062"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2012.03.021"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41413-022-00219-8"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.30375"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/S8756-3282(97)00154-3"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202002808RR"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2005.06.016"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-023-00970-w"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034512467803"}],"container-title":["Journal of Cellular and Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.70300","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T05:08:51Z","timestamp":1735621731000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jcmm.70300"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12]]},"references-count":63,"journal-issue":{"issue":"24","published-print":{"date-parts":[[2024,12]]}},"alternative-id":["10.1111\/jcmm.70300"],"URL":"https:\/\/doi.org\/10.1111\/jcmm.70300","archive":["Portico"],"relation":{},"ISSN":["1582-1838","1582-4934"],"issn-type":[{"value":"1582-1838","type":"print"},{"value":"1582-4934","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12]]},"assertion":[{"value":"2024-08-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70300"}}