{"doi":"10.1002/jcp.30314","title":"Mechanical loading attenuates breast cancer‐associated bone metastasis in obese mice by regulating the bone marrow microenvironment","abstract":"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-driven osteolysis, its effect on bone-metastasized obese mice has not been investigated. Here, we hypothesized that mechanical loading can lessen obesity-associated bone degradation in tumor-invaded bone by regulating the fate of bone marrow-derived cells. In this study, the effects of mechanical loading in obese mice were evaluated through X-ray 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-fat diet (HFD). However, mechanical loading markedly reduced these changes. It suppressed osteoclastogenesis by downregulating receptor activator of nuclear factor Kappa-B ligand and cathepsin K and promoted osteogenesis, which was associated with the upregulation of OPG and downregulation of C/enhancer-binding protein alpha and proliferator-activated receptor gamma for adipogenic differentiation. Furthermore, it decreased the levels of tumorigenic genes such as Rac1, MMP9, and interleukin 1β. In summary, this study demonstrates that although a HFD aggravates bone metastases associated with breast cancer, mechanical loading significantly protected tumor-invaded bone by regulating the fate of bone marrow-derived cells. The current study suggests that mechanical loading can provide a noninvasive, palliative option for alleviating breast cancer-associated bone metastasis, in particular for obese patients.","journal":"Journal of Cellular Physiology","year":2021,"id":183792,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9493,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":737668,"name":"Hong Liu","orcid":"0000-0001-8557-9549","position":1,"is_corresponding":false},{"id":737669,"name":"Lei Zhu","orcid":"0000-0003-0213-3619","position":2,"is_corresponding":false},{"id":344390,"name":"Xinle Li","orcid":"0000-0001-5747-4029","position":3,"is_corresponding":false},{"id":737670,"name":"Jie Li","orcid":"0000-0003-0837-5133","position":4,"is_corresponding":false},{"id":52597,"name":"Shuang Yang","orcid":"0000-0002-4779-8553","position":5,"is_corresponding":false},{"id":344393,"name":"Daquan Liu","orcid":"0000-0001-5949-0954","position":6,"is_corresponding":false},{"id":737671,"name":"Xiaomeng Song","orcid":"0000-0001-7103-6359","position":7,"is_corresponding":false},{"id":344395,"name":"Hiroki Yokota","orcid":"0000-0002-7881-8959","position":8,"is_corresponding":false},{"id":589364,"name":"Ping Zhang","orcid":"0000-0002-6336-6611","position":9,"is_corresponding":false},{"id":738143,"name":"Meng-lu Huang","orcid":null,"position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":null,"created_at":"2026-07-18T23:48:22.008011Z","pmid":"33554336","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}