{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T06:13:34Z","timestamp":1761718414926,"version":"build-2065373602"},"reference-count":51,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2015,8,28]],"date-time":"2015-08-28T00:00:00Z","timestamp":1440720000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Scientific Research (C) from the Ministry of Education, Culture, Sports, Science and Technology, Japan.","award":["No. 26462853"],"award-info":[{"award-number":["No. 26462853"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Osteolytic bone metastasis frequently occurs in the later stages of breast, lung, and several other cancers. Osteoclasts, the only cells that resorb bone, are hijacked by tumor cells, which break down bone remodeling systems. As a result, osteolysis occurs and may cause patients to suffer bone fractures, pain, and hypercalcemia. It is important to understand the mechanism of bone metastasis to establish new cancer therapies. MicroRNAs are small, noncoding RNAs that are involved in various biological processes, including cellular differentiation, proliferation, apoptosis, and tumorigenesis. MicroRNAs have significant clinical potential, including their use as new therapeutic targets and disease-specific biomarkers. Recent studies have revealed that microRNAs are involved in osteoclast differentiation and osteolytic bone metastasis. In this review focusing on microRNAs, the author discusses the roles of microRNAs in osteoclastogenesis and osteolytic bone metastasis.<\/jats:p>","DOI":"10.3390\/jcm4091741","type":"journal-article","created":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T10:55:58Z","timestamp":1441104958000},"page":"1741-1752","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["MicroRNAs and Osteolytic Bone Metastasis: The Roles of MicroRNAs in Tumor-Induced Osteoclast Differentiation"],"prefix":"10.3390","volume":"4","author":[{"given":"Tadayoshi","family":"Kagiya","sequence":"first","affiliation":[{"name":"Division of Functional Morphology, Department of Anatomy, Iwate Medical University, 2-1-1 Nishitokuta, Yahaba-cho, Iwate, 028-3694, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2015,8,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/j.tips.2015.04.006","article-title":"New therapeutic targets for cancer bone metastasis","volume":"36","author":"Krzeszinski","year":"2015","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/j.tem.2014.03.014","article-title":"MicroRNAs in the control of metastatic bone disease","volume":"25","author":"Browne","year":"2014","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1016\/j.ccr.2013.09.008","article-title":"Tumor-induced osteoclast miRNA changes as regulators and biomarkers of osteolytic bone metastasis","volume":"24","author":"Ell","year":"2013","journal-title":"Cancer Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.ccr.2013.10.001","article-title":"Cancer-associated osteoclast differentiation takes a good look in the miR(NA)ror","volume":"24","author":"Waning","year":"2013","journal-title":"Cancer Cell"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1111\/jre.12017","article-title":"Expression profiling of microRNAs in RAW264.7 cells treated with a combination of tumor necrosis factor alpha and RANKL during osteoclast differentiation","volume":"48","author":"Kagiya","year":"2013","journal-title":"J. Periodontal Res."},{"key":"ref_6","first-page":"142","article-title":"Expression of MicroRNAs in the Extracellular Microvesicles of Murine Osteoclasts","volume":"10","author":"Kagiya","year":"2013","journal-title":"J. Oral Tissue Engin."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"117","DOI":"10.4161\/sgtp.2.3.16453","article-title":"The regulation of osteoclast function and bone resorption by small GTPases","volume":"2","author":"Itzstein","year":"2011","journal-title":"Small GTPases"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1007\/s00774-009-0089-z","article-title":"Osteoclasts and the immune system","volume":"27","author":"Nakashima","year":"2009","journal-title":"J. Bone Miner. Metab."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/nrc3055","article-title":"Cancer to bone: a fatal attraction","volume":"11","author":"Weilbaecher","year":"2011","journal-title":"Nat. Rev. Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1038\/nature04524","article-title":"Regulation of cancer cell migration and bone metastasis by RANKL","volume":"440","author":"Jones","year":"2006","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2609","DOI":"10.1158\/1535-7163.MCT-07-0234","article-title":"Molecular biology of bone metastasis","volume":"6","author":"Kingsley","year":"2007","journal-title":"Mol. Cancer Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"10115","DOI":"10.3390\/molecules190710115","article-title":"MicroRNAs and bone metastasis: a new challenge","volume":"19","author":"Croset","year":"2014","journal-title":"Molecules"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1007\/s10585-008-9199-6","article-title":"Sinusoidal tumor angiogenesis is a key component in hepatocellular carcinoma metastasis","volume":"25","author":"Sugino","year":"2008","journal-title":"Clin. Exp. Metastasis"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1973","DOI":"10.1016\/S0002-9440(10)61147-9","article-title":"An invasion-independent pathway of blood-borne metastasis: a new murine mammary tumor model","volume":"160","author":"Sugino","year":"2002","journal-title":"Am. J. Pathol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1002\/path.2613","article-title":"Circulating tumour tissue fragments in patients with pulmonary metastasis of clear cell renal cell carcinoma","volume":"219","author":"Roodink","year":"2009","journal-title":"J. Pathol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1038\/71429","article-title":"Intravascular origin of metastasis from the proliferation of endothelium-attached tumor cells: a new model for metastasis","volume":"6","author":"Tozawa","year":"2000","journal-title":"Nat. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1038\/nrendo.2010.227","article-title":"Bone metastasis: mechanisms and therapeutic opportunities","volume":"7","author":"Suva","year":"2011","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4238","DOI":"10.1158\/0008-5472.CAN-11-3061","article-title":"Bone-derived IGF mediates crosstalk between bone and breast cancer cells in bony metastases","volume":"72","author":"Hiraga","year":"2012","journal-title":"Cancer Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1172\/JCI0217124","article-title":"Manipulating the environment of cancer cells in bone: a novel therapeutic approach","volume":"110","author":"Martin","year":"2002","journal-title":"J. Clin. Invest."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"598","DOI":"10.3390\/cancers7020598","article-title":"The Roles of MicroRNAs in Breast Cancer","volume":"7","author":"Takahashi","year":"2015","journal-title":"Cancers"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1002\/jcb.21335","article-title":"MicroRNA-223 is a key factor in osteoclast differentiation","volume":"101","author":"Sugatani","year":"2007","journal-title":"J. Cell Biochem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4667","DOI":"10.1074\/jbc.M805777200","article-title":"Impaired micro-RNA pathways diminish osteoclast differentiation and function","volume":"284","author":"Sugatani","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.bone.2013.07.007","article-title":"MicroRNA-124 regulates osteoclast differentiation","volume":"56","author":"Lee","year":"2013","journal-title":"Bone"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3648","DOI":"10.1182\/blood-2010-10-311415","article-title":"A microRNA expression signature of osteoclastogenesis","volume":"117","author":"Sugatani","year":"2011","journal-title":"Blood"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"15804","DOI":"10.1073\/pnas.0915022107","article-title":"miRNA-based mechanism for the commitment of multipotent progenitors to a single cellular fate","volume":"107","author":"Mann","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1002\/jcp.24306","article-title":"miR-29b negatively regulates human osteoclastic cell differentiation and function: implications for the treatment of multiple myeloma-related bone disease","volume":"228","author":"Rossi","year":"2013","journal-title":"J. Cell Physiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1002\/jbmr.2032","article-title":"MiR-503 regulates osteoclastogenesis via targeting RANK","volume":"29","author":"Chen","year":"2014","journal-title":"J. Bone Miner. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s13059-014-0561-5","article-title":"NF-kappaB-direct activation of microRNAs with repressive effects on monocyte-specific genes is critical for osteoclast differentiation","volume":"16","author":"Comet","year":"2015","journal-title":"Genome Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1038\/nature13375","article-title":"miR-34a blocks osteoporosis and bone metastasis by inhibiting osteoclastogenesis and Tgif2","volume":"512","author":"Krzeszinski","year":"2014","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e37361","DOI":"10.1371\/journal.pone.0037361","article-title":"Identification of microRNAs inhibiting TGF-beta-induced IL-11 production in bone metastatic breast cancer cells","volume":"7","author":"Pollari","year":"2012","journal-title":"PLoS One"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3756","DOI":"10.1016\/j.bbagen.2013.02.022","article-title":"MicroRNA-33a functions as a bone metastasis suppressor in lung cancer by targeting parathyroid hormone related protein","volume":"1830","author":"Kuo","year":"2013","journal-title":"Biochim. Biophys. Acta."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1186\/bcr2484","article-title":"MicroRNAs and their target gene networks in breast cancer","volume":"12","author":"Lal","year":"2010","journal-title":"Breast Cancer Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2124","DOI":"10.4161\/cc.9.11.11843","article-title":"miR-31: a crucial overseer of tumor metastasis and other emerging roles","volume":"9","author":"Valastyan","year":"2010","journal-title":"Cell Cycle"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"R102","DOI":"10.1186\/ar4282","article-title":"miR-31 controls osteoclast formation and bone resorption by targeting RhoA","volume":"15","author":"Mizoguchi","year":"2013","journal-title":"Arthritis Res. Ther."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.yexcr.2013.12.001","article-title":"MiR-125a TNF receptor-associated factor 6 to inhibit osteoclastogenesis","volume":"321","author":"Guo","year":"2014","journal-title":"Exp. Cell Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"E602","DOI":"10.1002\/ijc.29151","article-title":"MicroRNA-155 deficiency enhances the recruitment and functions of myeloid-derived suppressor cells in tumor microenvironment and promotes solid tumor growth","volume":"136","author":"Wang","year":"2015","journal-title":"Int. J. Cancer"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1016\/j.molonc.2014.01.012","article-title":"miRNA cargo within exosome-like vesicle transfer influences metastatic bone colonization","volume":"8","author":"Valencia","year":"2014","journal-title":"Mol. Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1550","DOI":"10.1158\/0008-5472.CAN-10-2372","article-title":"Gap junction-mediated import of microRNA from bone marrow stromal cells can elicit cell cycle quiescence in breast cancer cells","volume":"71","author":"Lim","year":"2011","journal-title":"Cancer Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1016\/j.bone.2012.10.033","article-title":"miR-326 associates with biochemical markers of bone turnover in lung cancer bone metastasis","volume":"52","author":"Valencia","year":"2013","journal-title":"Bone"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"20350","DOI":"10.1073\/pnas.0706901104","article-title":"MicroRNA-378 promotes cell survival, tumor growth, and angiogenesis by targeting SuFu and Fus-1 expression","volume":"104","author":"Lee","year":"2007","journal-title":"Proc. Natl Acad Sci USA"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1038\/ncb1596","article-title":"Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells","volume":"9","author":"Valadi","year":"2007","journal-title":"Nat. Cell. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"17442","DOI":"10.1074\/jbc.M110.107821","article-title":"Secretory mechanisms and intercellular transfer of microRNAs in living cells","volume":"285","author":"Kosaka","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"111","DOI":"10.3389\/fneur.2015.00111","article-title":"Microvesicles: What is the Role in Multiple Sclerosis?","volume":"6","author":"Carandini","year":"2015","journal-title":"Front Neurol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1849","DOI":"10.1007\/s00018-014-1811-0","article-title":"Interactions between cancer cells and normal cells via miRNAs in extracellular vesicles","volume":"72","author":"Ochiya","year":"2015","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"20677","DOI":"10.3402\/jev.v2i0.20677","article-title":"Distinct RNA profiles in subpopulations of extracellular vesicles: apoptotic bodies, microvesicles and exosomes","volume":"2","author":"Crescitelli","year":"2013","journal-title":"J. Extracell Vesicles"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"20389","DOI":"10.3402\/jev.v2i0.20389","article-title":"As we wait: coping with an imperfect nomenclature for extracellular vesicles","volume":"2","author":"Gould","year":"2013","journal-title":"J. Extracell Vesicles"},{"key":"ref_47","unstructured":"Rogers, J.V. (2014). Microarrays: Principles, Applications and Technologies, Nova Science Publishers."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"5003","DOI":"10.1073\/pnas.1019055108","article-title":"Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma","volume":"108","author":"Arroyo","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"13772","DOI":"10.18632\/oncotarget.3830","article-title":"Involvement of multiple myeloma cell-derived exosomes in osteoclast differentiation","volume":"6","author":"Raimondi","year":"2015","journal-title":"Oncotarget"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.bone.2015.05.022","article-title":"Osteoblast-derived microvesicles: A novel mechanism for communication between osteoblasts and osteoclasts","volume":"79","author":"Deng","year":"2015","journal-title":"Bone"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1038\/nature07228","article-title":"Widespread changes in protein synthesis induced by microRNAs","volume":"455","author":"Selbach","year":"2008","journal-title":"Nature"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/4\/9\/1741\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T20:47:40Z","timestamp":1760215660000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/4\/9\/1741"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,8,28]]},"references-count":51,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2015,9]]}},"alternative-id":["jcm4091741"],"URL":"https:\/\/doi.org\/10.3390\/jcm4091741","relation":{},"ISSN":["2077-0383"],"issn-type":[{"type":"electronic","value":"2077-0383"}],"subject":[],"published":{"date-parts":[[2015,8,28]]}}}