{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T15:09:34Z","timestamp":1787843374506,"version":"build-2784847793"},"reference-count":61,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2016,8,11]],"date-time":"2016-08-11T00:00:00Z","timestamp":1470873600000},"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":["26462853"],"award-info":[{"award-number":["26462853"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Periodontal disease is an inflammatory disease caused by bacterial infection of tooth-supporting structures, which results in the destruction of alveolar bone. Osteoclasts play a central role in bone destruction. Osteoclasts are tartrate-resistant acid phosphatase (TRAP)-positive multinucleated giant cells derived from hematopoietic stem cells. Recently, we and other researchers revealed that microRNAs are involved in osteoclast differentiation. MicroRNAs are novel, single-stranded, non-coding, small (20\u201322 nucleotides) RNAs that act in a sequence-specific manner to regulate gene expression at the post-transcriptional level through cleavage or translational repression of their target mRNAs. They regulate various biological activities such as cellular differentiation, apoptosis, cancer development, and inflammatory responses. In this review, the roles of microRNAs in osteoclast differentiation and function during alveolar bone destruction in periodontal disease are described.<\/jats:p>","DOI":"10.3390\/ijms17081317","type":"journal-article","created":{"date-parts":[[2016,8,11]],"date-time":"2016-08-11T10:29:29Z","timestamp":1470911369000},"page":"1317","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["MicroRNAs: Potential Biomarkers and Therapeutic Targets for Alveolar Bone Loss in Periodontal Disease"],"prefix":"10.3390","volume":"17","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":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2016,8,11]]},"reference":[{"key":"ref_1","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 \u03b1 and RANKL during osteoclast differentiation","volume":"48","author":"Kagiya","year":"2013","journal-title":"J. Periodontal Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.3390\/jcm4091741","article-title":"MicroRNAs and osteolytic bone metastasis: The roles of microRNAs in tumor-induced osteoclast differentiation","volume":"4","author":"Kagiya","year":"2015","journal-title":"J. Clin. Med."},{"key":"ref_3","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_4","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/0092-8674(93)90529-Y","article-title":"The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14","volume":"75","author":"Lee","year":"1993","journal-title":"Cell"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1016\/0092-8674(93)90530-4","article-title":"Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans","volume":"75","author":"Wightman","year":"1993","journal-title":"Cell"},{"key":"ref_6","unstructured":"Reeves, C. (2015). Osteoclasts: Cell Biology, Functions and Related Disease, Nova Science Publishers."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1177\/0022034511425045","article-title":"MicroRNA modulation in obesity and periodontitis","volume":"91","author":"Perri","year":"2012","journal-title":"J. Dent. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"43","DOI":"10.32604\/biocell.2011.35.043","article-title":"Comparison of inflammatory microRNA expression in healthy and periodontitis tissues","volume":"35","author":"Lee","year":"2011","journal-title":"Biocell"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"125","DOI":"10.4248\/IJOS11046","article-title":"Comparison of microRNA profiles of human periodontal diseased and healthy gingival tissues","volume":"3","author":"Xie","year":"2011","journal-title":"Int. J. Oral Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1177\/0022034512456551","article-title":"MicroRNAs and their target genes in gingival tissues","volume":"91","author":"Guarnieri","year":"2012","journal-title":"J. Dent. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"253","DOI":"10.2334\/josnusd.56.253","article-title":"MicroRNA expression in inflamed and noninflamed gingival tissues from Japanese patients","volume":"56","author":"Ogata","year":"2014","journal-title":"J. Oral Sci."},{"key":"ref_12","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_13","doi-asserted-by":"crossref","first-page":"3531","DOI":"10.1007\/s00018-015-1940-0","article-title":"MicroRNA: Master controllers of intracellular signaling pathways","volume":"72","author":"Lui","year":"2015","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.molcel.2007.06.017","article-title":"MicroRNA targeting specificity in mammals: Determinants beyond seed pairing","volume":"27","author":"Grimson","year":"2007","journal-title":"Mol. Cell"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1111\/jre.12193","article-title":"Lipopolysaccharide-regulated production of bone sialoprotein and interleukin-8 in human periodontal ligament fibroblasts: The role of toll-like receptors 2 and 4 and the MAPK pathway","volume":"50","author":"Zhang","year":"2015","journal-title":"J. Periodontal Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/ni.1828","article-title":"Negative regulation of TLR4 via targeting of the proinflammatory tumor suppressor PDCD4 by the microRNA miR-21","volume":"11","author":"Sheedy","year":"2010","journal-title":"Nat. Immunol."},{"key":"ref_17","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_18","doi-asserted-by":"crossref","first-page":"48","DOI":"10.3389\/fimmu.2014.00048","article-title":"Classical and paradoxical effects of TNF-\u03b1 on bone homeostasis","volume":"5","author":"Osta","year":"2014","journal-title":"Front. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1002\/jcb.22243","article-title":"miR-29 suppression of osteonectin in osteoblasts: Regulation during differentiation and by canonical Wnt signaling","volume":"108","author":"Kapinas","year":"2009","journal-title":"J. Cell. Biochem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"15676","DOI":"10.1074\/jbc.M809787200","article-title":"Biological functions of miR-29b contribute to positive regulation of osteoblast differentiation","volume":"284","author":"Li","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1093\/jmcb\/mjr007","article-title":"MicroRNAs in NF-\u03baB signaling","volume":"3","author":"Ma","year":"2011","journal-title":"J. Mol. Cell. Biol."},{"key":"ref_22","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_23","doi-asserted-by":"crossref","first-page":"33347","DOI":"10.1074\/jbc.M113.484568","article-title":"miR-29 promotes murine osteoclastogenesis by regulating osteoclast commitment and migration","volume":"288","author":"Franceschetti","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_24","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_25","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_26","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_27","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_28","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1136\/annrheumdis-2014-206417","article-title":"MicroRNA-124 inhibits the progression of adjuvant-induced arthritis in rats","volume":"75","author":"Nakamachi","year":"2016","journal-title":"Ann. Rheum. Dis."},{"key":"ref_29","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_30","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s13059-014-0561-5","article-title":"NF-\u03baB-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_31","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_32","doi-asserted-by":"crossref","first-page":"12481","DOI":"10.1073\/pnas.0605298103","article-title":"NF-\u03baB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses","volume":"103","author":"Taganov","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1002\/art.30321","article-title":"The inhibitory effect of microRNA-146a expression on bone destruction in collagen-induced arthritis","volume":"63","author":"Nakasa","year":"2011","journal-title":"Arthritis Rheum."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1016\/j.bbrc.2012.03.102","article-title":"Porphyromonas gingivalis lipopolysaccharide I nduces miR-146a without altering the production of inflammatory cytokines","volume":"420","author":"Honda","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"10721","DOI":"10.1038\/srep10721","article-title":"Biodistribution and function of extracellular miRNA-155 in mice","volume":"5","author":"Bala","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2325","DOI":"10.1902\/jop.2007.070135","article-title":"Gingival crevicular fluid levels of leukotriene B4 in periodontal health and disease","volume":"78","author":"Pradeep","year":"2007","journal-title":"J. Periodontol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2349","DOI":"10.4049\/jimmunol.1302982","article-title":"Leukotriene B4 enhances the generation of proinflammatory microRNAs to promote MyD88-dependent macrophage activation","volume":"192","author":"Wang","year":"2014","journal-title":"J. Immunol."},{"key":"ref_38","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_39","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1002\/jcb.22228","article-title":"Osteoclast-specific Dicer gene deficiency suppresses osteoclastic bone resorption","volume":"109","author":"Mizoguchi","year":"2010","journal-title":"J. Cell. Biochem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1002\/art.30281","article-title":"Essential role of microRNA-155 in the pathogenesis of autoimmune arthritis in mice","volume":"63","author":"Bluml","year":"2011","journal-title":"Arthritis Rheum."},{"key":"ref_41","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_42","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_43","doi-asserted-by":"crossref","first-page":"2202","DOI":"10.1016\/j.bbadis.2015.08.003","article-title":"High inorganic phosphate concentration inhibits osteoclastogenesis by modulating miR-223","volume":"1852","author":"Louvet","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1002\/jcb.24471","article-title":"Down-regulation of miR-21 biogenesis by estrogen action contributes to osteoclastic apoptosis","volume":"114","author":"Sugatani","year":"2013","journal-title":"J. Cell. Biochem."},{"key":"ref_45","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_46","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1002\/jbmr.1845","article-title":"miR-148a regulates osteoclastogenesis by targeting V-maf musculoaponeurotic fibrosarcoma oncogene homolog B","volume":"28","author":"Cheng","year":"2013","journal-title":"J. Bone Miner Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.bonr.2015.06.003","article-title":"Osteoporotic bone of miR-150-deficient mice: Possibly due to low serum OPG-mediated osteoclast activation","volume":"3","author":"Choi","year":"2015","journal-title":"Bone Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3255","DOI":"10.1016\/j.febslet.2012.06.047","article-title":"Interferon-\u03b2-induced miR-155 inhibits osteoclast differentiation by targeting SOCS1 and MITF","volume":"586","author":"Zhang","year":"2012","journal-title":"FEBS Lett."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"27066","DOI":"10.3402\/jev.v4.27066","article-title":"Biological properties of extracellular vesicles and their physiological functions","volume":"4","author":"Siljander","year":"2015","journal-title":"J. Extracell. Vesicles"},{"key":"ref_50","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_51","doi-asserted-by":"crossref","unstructured":"Crescitelli, R., Lasser, C., Szabo, T.G., Kittel, A., Eldh, M., Dianzani, I., Buzas, E.I., and Lotvall, J. (2013). Distinct RNA profiles in subpopulations of extracellular vesicles: Apoptotic bodies, microvesicles and exosomes. J. Extracell. Vesicles, 2.","DOI":"10.3402\/jev.v2i0.20677"},{"key":"ref_52","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_53","doi-asserted-by":"crossref","unstructured":"Gould, S.J., and Raposo, G. (2013). As we wait: Coping with an imperfect nomenclature for extracellular vesicles. J. Extracell. Vesicles, 2.","DOI":"10.3402\/jev.v2i0.20389"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1038\/sj.leu.2404132","article-title":"Embryonic stem cell-derived microvesicles reprogram hematopoietic progenitors: Evidence for horizontal transfer of mRNA and protein delivery","volume":"20","author":"Ratajczak","year":"2006","journal-title":"Leukemia"},{"key":"ref_55","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_56","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_57","unstructured":"Rogers, J.V. (2014). Microarrays: Principles, Applications and Technologies, Nova Science Publishers."},{"key":"ref_58","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 Eng."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/s13148-015-0083-3","article-title":"Inflammation triggers specific microRNA profiles in human adipocytes and macrophages and in their supernatants","volume":"7","author":"Ortega","year":"2015","journal-title":"Clin. Epigenet."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"7321","DOI":"10.1038\/ncomms8321","article-title":"Exosome-delivered microRNAs modulate the inflammatory response to endotoxin","volume":"6","author":"Alexander","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.bbrc.2010.02.145","article-title":"Serum miR-146a and miR-223 as potential new biomarkers for sepsis","volume":"394","author":"Wang","year":"2010","journal-title":"Biochem. Biophys. Res. Commun."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/17\/8\/1317\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T19:28:16Z","timestamp":1760210896000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/17\/8\/1317"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,8,11]]},"references-count":61,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2016,8]]}},"alternative-id":["ijms17081317"],"URL":"https:\/\/doi.org\/10.3390\/ijms17081317","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,8,11]]}}}