{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T08:08:12Z","timestamp":1768723692463,"version":"3.49.0"},"reference-count":26,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2019,4,11]],"date-time":"2019-04-11T00:00:00Z","timestamp":1554940800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Office of the Assistant Secretary of Defense for Health Affairs","award":["12-1-0400"],"award-info":[{"award-number":["12-1-0400"]}]},{"name":"Office of the Assistant Secretary of Defense for Health Affairs","award":["Award No."],"award-info":[{"award-number":["Award No."]}]},{"name":"National Institute of Health","award":["grant R21 AR060452"],"award-info":[{"award-number":["grant R21 AR060452"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Chemokines are secreted by a wide variety of cells; their functions are dependent on the binding to their chemokine receptors (CCRs) which induce directed chemotaxis in nearby responsive cells. Chemokines and their receptors can be induced under several different conditions. Based on data from clinical studies showing an increased expression of chemokine receptor 3 (CCR3) in circulating monocytes of human subjects with lower bone mineral density (BMD) as compared to those with high BMD, we predicted a role for CCR3 in the development of peak bone mass. We, therefore, first evaluated the expression pattern of <jats:italic>Ccr3<\/jats:italic> in bone cells, in comparison to other CCRs, that have common ligands with CCR3. While <jats:italic>Ccr1<\/jats:italic> and <jats:italic>Ccr<\/jats:italic>3 messenger RNA (mRNA) levels increased during both RANKL\u2010induced osteoclast differentiation and AA\u2010induced osteoblast differentiation, the levels of <jats:italic>Ccr<\/jats:italic>5 mRNA only increased during osteoblast differentiation. To examine if CCR3 influences osteoclast and\/or osteoblast differentiation, we evaluated the consequence of blocking CCR3 function using neutralizing antibody on the expression of osteoclast and osteoblast differentiation markers. Treatment with CCR3 neutralizing antibody increased mRNA levels of Trap and cathepsin K in osteoclasts and osteocalcin in osteoblasts compared to cells treated with control IgG. Based on these in vitro findings, we next assessed the role of CCR3 in vivo by evaluating the skeletal phenotypes of <jats:italic>Ccr3<\/jats:italic> knockout and corresponding control littermate mice. Disruption of CCR3 resulted in a significant increase in femur areal BMD at 5 and 8 weeks of age by dual\u2010energy X\u2010ray absorptiometry. Micro\u2010CT analysis revealed a 25% increase in trabecular bone mass at 10 weeks of age caused by corresponding changes in trabecular number and thickness compared to wild type mice. Based on our findings, we conclude that disruption of CCR3 function favors bone mass accumulation, in part via enhancement of bone metabolism. Understanding the molecular pathways through which CCR3 acts to regulate osteoclast and osteoblast functions could lead to new therapeutic approaches to prevent inflammation\u2010induced bone loss.<\/jats:p>","DOI":"10.1002\/jcb.28672","type":"journal-article","created":{"date-parts":[[2019,4,12]],"date-time":"2019-04-12T10:36:35Z","timestamp":1555065395000},"page":"13974-13984","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Chemokine receptor 3 is a negative regulator of trabecular bone mass in female mice"],"prefix":"10.1002","volume":"120","author":[{"given":"Subburaman","family":"Mohan","sequence":"first","affiliation":[{"name":"Musculoskeletal Disease Center Research Service, LLVARE, Jerry L. Pettis Memorial VA Medical Center Loma Linda California"},{"name":"Department of Medicine Loma Linda University Loma Linda California"},{"name":"Department of Biochemistry Loma Linda University Loma Linda California"},{"name":"Department of Physiology Loma Linda University Loma Linda California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Hu","sequence":"additional","affiliation":[{"name":"Musculoskeletal Disease Center Research Service, LLVARE, Jerry L. Pettis Memorial VA Medical Center Loma Linda California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6407-9411","authenticated-orcid":false,"given":"Bouchra","family":"Edderkaoui","sequence":"additional","affiliation":[{"name":"Musculoskeletal Disease Center Research Service, LLVARE, Jerry L. Pettis Memorial VA Medical Center Loma Linda California"},{"name":"Department of Medicine Loma Linda University Loma Linda California"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,4,11]]},"reference":[{"key":"e_1_2_7_1_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2010.190"},{"key":"e_1_2_7_1_3_1","doi-asserted-by":"publisher","DOI":"10.1677\/JOE-08-0568"},{"key":"e_1_2_7_1_4_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/615486"},{"key":"e_1_2_7_1_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2017.00467"},{"key":"e_1_2_7_1_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2008.04.009"},{"key":"e_1_2_7_1_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4419-9129-4_4"},{"key":"e_1_2_7_1_8_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.2003.04561.x"},{"key":"e_1_2_7_1_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra052723"},{"key":"e_1_2_7_1_10_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.111.005074"},{"key":"e_1_2_7_1_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4652(200005)183:2<196::AID-JCP6>3.0.CO;2-8"},{"key":"e_1_2_7_1_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.1937"},{"key":"e_1_2_7_1_13_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2005-0065"},{"key":"e_1_2_7_1_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.099424"},{"key":"e_1_2_7_1_15_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M501164200"},{"key":"e_1_2_7_1_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.261462598"},{"key":"e_1_2_7_1_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0114357"},{"key":"e_1_2_7_1_18_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.6009507"},{"key":"e_1_2_7_1_19_1","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_2_7_1_20_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.90203.2008"},{"key":"e_1_2_7_1_21_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.142.10.8436"},{"key":"e_1_2_7_1_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S8756-3282(02)00738-X"},{"key":"e_1_2_7_1_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-012-9687-1"},{"key":"e_1_2_7_1_24_1","doi-asserted-by":"publisher","DOI":"10.4065\/76.3.295"},{"key":"e_1_2_7_1_25_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.040910"},{"key":"e_1_2_7_1_26_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.154.11.6065"},{"key":"e_1_2_7_1_27_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-6122"}],"container-title":["Journal of Cellular Biochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcb.28672","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcb.28672","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcb.28672","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcb.28672","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,10]],"date-time":"2024-09-10T11:18:00Z","timestamp":1725967080000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcb.28672"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4,11]]},"references-count":26,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2019,8]]}},"alternative-id":["10.1002\/jcb.28672"],"URL":"https:\/\/doi.org\/10.1002\/jcb.28672","archive":["Portico"],"relation":{},"ISSN":["0730-2312","1097-4644"],"issn-type":[{"value":"0730-2312","type":"print"},{"value":"1097-4644","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,4,11]]},"assertion":[{"value":"2018-07-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-02-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-04-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}