{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T05:33:56Z","timestamp":1788845636863,"version":"build-2803163510"},"reference-count":48,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2021,2,7]],"date-time":"2021-02-07T00:00:00Z","timestamp":1612656000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100006606","name":"Natural Science Foundation of Tianjin City","doi-asserted-by":"publisher","award":["81772405, 81572100"],"award-info":[{"award-number":["81772405, 81572100"]}],"id":[{"id":"10.13039\/501100006606","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Breast cancer, a common malignancy for women, preferentially metastasizes to bone and obesity elevates the chance of its progression. While mechanical loading can suppress obesity and tumor\u2010driven osteolysis, its effect on bone\u2010metastasized obese mice has not been investigated. Here, we hypothesized that mechanical loading can lessen obesity\u2010associated bone degradation in tumor\u2010invaded bone by regulating the fate of bone marrow\u2010derived cells. In this study, the effects of mechanical loading in obese mice were evaluated through X\u2010ray imaging, histology, cytology, and molecular analyses. Tumor inoculation to the tibia elevated body fat composition, osteolytic lesions, and tibia destruction, and these pathologic changes were stimulated by the high\u2010fat diet (HFD). However, mechanical loading markedly reduced these changes. It suppressed osteoclastogenesis by downregulating receptor activator of nuclear factor Kappa\u2010B ligand and cathepsin K and promoted osteogenesis, which was associated with the upregulation of OPG and downregulation of C\/enhancer\u2010binding protein alpha and proliferator\u2010activated receptor gamma for adipogenic differentiation. Furthermore, it decreased the levels of tumorigenic genes such as Rac1, MMP9, and interleukin 1\u03b2. In summary, this study demonstrates that although a HFD aggravates bone metastases associated with breast cancer, mechanical loading significantly protected tumor\u2010invaded bone by regulating the fate of bone marrow\u2010derived cells. The current study suggests that mechanical loading can provide a noninvasive, palliative option for alleviating breast cancer\u2010associated bone metastasis, in particular for obese patients.<\/jats:p>","DOI":"10.1002\/jcp.30314","type":"journal-article","created":{"date-parts":[[2021,2,8]],"date-time":"2021-02-08T20:17:54Z","timestamp":1612815474000},"page":"6391-6406","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Mechanical loading attenuates breast cancer\u2010associated bone metastasis in obese mice by regulating the bone marrow microenvironment"],"prefix":"10.1002","volume":"236","author":[{"given":"Menglu","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Anatomy and Histology, School of Basic Medical Sciences Tianjin Medical University Tianjin China"},{"name":"Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases Tianjin Medical University Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, National Clinical Research Center for Cancer Tianjin Medical University Cancer Institute and Hospital Tianjin China"},{"name":"Key Laboratory of Cancer Prevention and Therapy Tianjin China"},{"name":"Tianjin's Clinical Research Center for Cancer Tianjin China"},{"name":"Key Laboratory of Cancer Prevention and Therapy Tianjin Medical University, Ministry of Education Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Zhu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Cancer Prevention and Therapy Tianjin China"},{"name":"Department of Molecular Imaging and Nuclear Medicine, National Clinical Research Center for Cancer Tianjin Medical University Cancer Institute and Hospital Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinle","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Histology, School of Basic Medical Sciences Tianjin Medical University Tianjin China"},{"name":"Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases Tianjin Medical University Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Histology, School of Basic Medical Sciences Tianjin Medical University Tianjin China"},{"name":"Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases Tianjin Medical University Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Histology, School of Basic Medical Sciences Tianjin Medical University Tianjin China"},{"name":"Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases Tianjin Medical University Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daquan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Histology, School of Basic Medical Sciences Tianjin Medical University Tianjin China"},{"name":"Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases Tianjin Medical University Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomeng","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Histology, School of Basic Medical Sciences Tianjin Medical University Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7881-8959","authenticated-orcid":false,"given":"Hiroki","family":"Yokota","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Indiana University\u2013Purdue University Indianapolis Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6336-6611","authenticated-orcid":false,"given":"Ping","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Histology, School of Basic Medical Sciences Tianjin Medical University Tianjin China"},{"name":"Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases Tianjin Medical University Tianjin China"},{"name":"Department of Biomedical Engineering Indiana University\u2013Purdue University Indianapolis Indianapolis Indiana USA"},{"name":"Tianjin Key Laboratory of Spine and Spinal Cord Tianjin Medical University Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,2,7]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200419900"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-018-0134-8"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2020.03.033"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S209056"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.2147\/CMAR.S182510"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19124041"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/2946409"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2008.00606.x"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.00462"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.12917"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.125543"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-018-1001-2"},{"issue":"3","key":"e_1_2_9_14_1","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1515\/hmbci-2013-0036","article-title":"Adipose tissue and bone: role of PPAR\u03b3 in adipogenesis and osteogenesis","volume":"15","author":"Kawai M.","year":"2013","journal-title":"Horm Mol Biol Clin Investig"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-019-2159-z"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201802711R"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep24668"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2013.348"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.4162\/nrp.2015.9.6.599"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2015.09.012"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-05488-6"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2019.00617"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12071812"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbo.2016.03.006"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-020-05613-6"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.30825"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2014.01.009"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21405"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.22232"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.15152"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.2174\/1871520618666180611112125"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.3861"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21144967"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.5483\/BMBRep.2019.52.8.116"},{"issue":"1","key":"e_1_2_9_35_1","first-page":"167","article-title":"Bone marrow mesenchymal stem cells suppress ascitogenous hepatoma progression in BALB\/c mouse through reducing myeloid\u2010derived suppressor cells","volume":"25","author":"Su X.","year":"2015","journal-title":"Biomedical Materials and Engineering"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2009.137"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/hepr.13076"},{"issue":"2","key":"e_1_2_9_38_1","first-page":"2151","article-title":"Knockdown of RAC1 and VASP gene expression inhibits breast cancer cell migration","volume":"16","author":"Tian Y.","year":"2018","journal-title":"Oncology Letters"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2019.06.003"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.00076"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S206695"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/gt.2014.110"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201900306RR"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2474-14-197"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1097\/JES.0b013e31819121c6"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjsm.2007.042556"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2006.09.018"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201801851R"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaw6143"}],"container-title":["Journal of Cellular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcp.30314","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcp.30314","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcp.30314","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,23]],"date-time":"2024-08-23T20:53:38Z","timestamp":1724446418000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcp.30314"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,7]]},"references-count":48,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2021,9]]}},"alternative-id":["10.1002\/jcp.30314"],"URL":"https:\/\/doi.org\/10.1002\/jcp.30314","archive":["Portico"],"relation":{},"ISSN":["0021-9541","1097-4652"],"issn-type":[{"value":"0021-9541","type":"print"},{"value":"1097-4652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,7]]},"assertion":[{"value":"2020-08-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-01-25","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-02-07","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}