{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T04:24:26Z","timestamp":1772252666935,"version":"3.50.1"},"reference-count":41,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2016,12,27]],"date-time":"2016-12-27T00:00:00Z","timestamp":1482796800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Japan Society for the Promotion of Science, a Grant-in-Aid for Scientific Research (C)","award":["25463231"],"award-info":[{"award-number":["25463231"]}]},{"name":"Japan Society for the Promotion of Science, a Grant-in-Aid for Scientific Research (C)","award":["26462982"],"award-info":[{"award-number":["26462982"]}]},{"name":"Japan Society for the Promotion of Science, a Grant-in-Aid for Yooung Scientists (B)","award":["15K20491"],"award-info":[{"award-number":["15K20491"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The present study was performed to examine how transforming growth factor \u03b2 (TGF-\u03b2) in root-surrounding tissues on deciduous teeth regulates the differentiation induction into odontoclasts during physiological root resorption. We prepared root-surrounding tissues with (R) or without (N) physiological root resorption scraped off at three regions (R1\u2013R3 or N1\u2013N3) from the cervical area to the apical area of the tooth and measured both TGF-\u03b2 and the tartrate-resistant acid phosphatase (TRAP) activities. The TGF-\u03b2 activity level was increased in N1\u2013N3, whereas the TRAP activity was increased in R2 and R3. In vitro experiments for the receptor activator of nuclear factor-\u03baB (NF-\u03baB) ligand (RANKL)-mediated osteoclast differentiation revealed that proteins from N1\u2013N3 and R1\u2013R3 enhanced the TRAP activity in RAW264 cells. A genetic study indicated that the mRNA levels of TGF-\u03b21 in N1 and N2 were significantly increased, and corresponded with levels of osteoprotegerin (OPG). In contrast, the expression level of RANKL was increased in R2 and R3. Our findings suggest that TGF-\u03b2 is closely related to the regulation of OPG induction and RANKL-mediated odontoclast differentiation depending on the timing of RANKL and OPG mRNA expression in the root-surrounding tissues of deciduous teeth during physiological root resorption.<\/jats:p>","DOI":"10.3390\/ijms18010049","type":"journal-article","created":{"date-parts":[[2016,12,28]],"date-time":"2016-12-28T11:22:14Z","timestamp":1482924134000},"page":"49","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["TGF-\u03b2 and Physiological Root Resorption of Deciduous Teeth"],"prefix":"10.3390","volume":"18","author":[{"given":"Emi","family":"Shimazaki","sequence":"first","affiliation":[{"name":"Department of Pediatric Dentistry, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama 230-8501, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeo","family":"Karakida","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama 230-8501, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryuji","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama 230-8501, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saeko","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Pediatric Dentistry, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama 230-8501, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Makoto","family":"Fukae","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama 230-8501, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuo","family":"Yamakoshi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama 230-8501, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshinobu","family":"Asada","sequence":"additional","affiliation":[{"name":"Department of Pediatric Dentistry, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama 230-8501, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2016,12,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1177\/00220345860650080901","article-title":"An ultrastructural study of tooth resorption in the kitten","volume":"65","author":"Anderson","year":"1986","journal-title":"J. Dent. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1002\/aja.1001830404","article-title":"Dentin resorption mediated by odontoclasts in physiological root resorption of human deciduous teeth","volume":"183","author":"Sasaki","year":"1988","journal-title":"Am. J. Anat."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1002\/ar.1092240307","article-title":"Multinucleated cells formed on calcified dentine from mouse bone marrow cells treated with 1\u03b1,25-dihydroxyvitamin D3 have ruffled borders and resorb dentine","volume":"224","author":"Sasaki","year":"1989","journal-title":"Anat. Rec."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1007\/BF01004735","article-title":"Enzyme histochemical characteristics of human and kitten odontoclasts and kitten osteoclasts: A comparative study using whole cells","volume":"11","author":"Addison","year":"1979","journal-title":"Histochem. J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1002\/ar.1127","article-title":"Immunolocalization of vacuolar-type H+-ATPase, cathepsin K, matrix metalloproteinase-9, and receptor activator of NF-\u03baB ligand in odontoclasts during physiological root resorption of human deciduous teeth","volume":"264","author":"Oshiro","year":"2001","journal-title":"Anat. Rec."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3597","DOI":"10.1073\/pnas.95.7.3597","article-title":"Osteoclast differentiation factor is a ligand for osteoprotegerin\/osteoclastogenesis-inhibitory factor and is identical to TRANCE\/RANKL","volume":"95","author":"Yasuda","year":"1998","journal-title":"Proc. Nat. Acad. Sci. USA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/S0092-8674(00)80209-3","article-title":"Osteoprotegerin: A novel secreted protein involved in the regulation of bone density","volume":"89","author":"Simonet","year":"1997","journal-title":"Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1177\/00220345010800030801","article-title":"Dual regulation of osteoclast differentiation by periodontal ligament cells through RANKL stimulation and OPG inhibition","volume":"80","author":"Kanzaki","year":"2001","journal-title":"J. Dent. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1902\/jop.2004.75.9.1247","article-title":"The role of parathyroid hormone-related protein in the regulation of osteoclastogenesis by cementoblasts","volume":"75","author":"Boabaid","year":"2004","journal-title":"J. Periodontol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1111\/jre.12131","article-title":"Tumor necrosis factor-\u03b1 enhances RANKL expression in gingival epithelial cells via protein kinase a signaling","volume":"49","author":"Fujihara","year":"2014","journal-title":"J. Periodontal Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"36241","DOI":"10.1074\/jbc.M104319200","article-title":"Stimulation of osteoprotegerin (OPG) gene expression by transforming growth factor-\u03b2 (TGF-\u03b2). Mapping of the opg promoter region that mediates TGF-\u03b2 effects","volume":"276","author":"Thirunavukkarasu","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1002\/jcp.24122","article-title":"Deciduous dental pulp stem cells are involved in osteoclastogenesis during physiologic root resorption","volume":"228","author":"Zhu","year":"2013","journal-title":"J. Cell. Physiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1177\/154411130201300403","article-title":"Cellular, molecular, and genetic determinants of tooth eruption","volume":"13","author":"Wise","year":"2002","journal-title":"Crit. Rev. Oral Biol. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"7296","DOI":"10.1073\/pnas.110553397","article-title":"Parathyroid hormone-related protein induces spontaneous osteoclast formation via a paracrine cascade","volume":"97","author":"Nakchbandi","year":"2000","journal-title":"Proc. Nat. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"24","DOI":"10.2329\/perio.52.24","article-title":"Growth and differentiation factors exist in porcine periodontal ligament tissues","volume":"52","author":"Matsushima","year":"2010","journal-title":"J. Jpn. Soc. Periodontol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5737","DOI":"10.1021\/bi500647d","article-title":"Biological activity differences between TGF-\u03b21 and TGF-\u03b23 correlate with differences in the rigidity and arrangement of their component monomers","volume":"53","author":"Huang","year":"2014","journal-title":"Biochemistry"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"27091","DOI":"10.1074\/jbc.273.42.27091","article-title":"Transforming growth factor-\u03b2 stimulates the production of osteoprotegerin\/osteoclastogenesis inhibitory factor by bone marrow stromal cells","volume":"273","author":"Takai","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1006\/bbrc.1998.9723","article-title":"Transforming growth factor-\u03b21 increases mrna levels of osteoclastogenesis inhibitory factor in osteoblastic\/stromal cells and inhibits the survival of murine osteoclast-like cells","volume":"252","author":"Murakami","year":"1998","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1006\/bbrc.1999.1632","article-title":"TGF-\u03b2 enhances osteoclast differentiation in hematopoietic cell cultures stimulated with RANKL and M-CSF","volume":"265","author":"Gatlin","year":"1999","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1359\/jbmr.2001.16.10.1787","article-title":"Transforming growth factor \u03b2 affects osteoclast differentiation via direct and indirect actions","volume":"16","author":"Quinn","year":"2001","journal-title":"J. Bone Miner. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/S0898-6568(01)00221-2","article-title":"Role of TGF-\u03b2 family in osteoclastogenesis induced by RANKL","volume":"14","author":"Koseki","year":"2002","journal-title":"Cell Signal."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1002\/jbmr.357","article-title":"Regulation of RANKL-induced osteoclastogenesis by TGF-\u03b2 through molecular interaction between SMAD3 and TRAF6","volume":"26","author":"Yasui","year":"2011","journal-title":"J. Bone Miner. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3745","DOI":"10.1210\/en.2013-1272","article-title":"TGF-\u03b2 induces Wnt10b in osteoclasts from female mice to enhance coupling to osteoblasts","volume":"154","author":"Ota","year":"2013","journal-title":"Endocrinology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"33644","DOI":"10.1038\/srep33644","article-title":"TGF-\u03b21 autocrine signalling and enamel matrix components","volume":"6","author":"Yamakoshi","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1177\/0022034514534690","article-title":"DPP and DSP are necessary for maintaining TGF-\u03b21 activity in dentin","volume":"93","author":"Yamakoshi","year":"2014","journal-title":"J. Dent. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1042\/bj3020527","article-title":"Interaction of the small interstitial proteoglycans biglycan, decorin and fibromodulin with transforming growth factor \u03b2","volume":"302","author":"Hildebrand","year":"1994","journal-title":"Biochem. J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1096\/fasebj.10.5.8621059","article-title":"Proteoglycans of the extracellular environment: Clues from the gene and protein side offer novel perspectives in molecular diversity and function","volume":"10","author":"Iozzo","year":"1996","journal-title":"FASEB J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1080\/10408360490460933","article-title":"Latent TGF-\u03b2 binding proteins: Extracellular matrix association and roles in TGF-\u03b2 activation","volume":"41","author":"Hyytiainen","year":"2004","journal-title":"Crit. Rev. Clin. Lab. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1007\/s00223-009-9248-4","article-title":"TGF-\u03b2\/extracellular matrix interactions in dentin matrix: A role in regulating sequestration and protection of bioactivity","volume":"85","author":"Baker","year":"2009","journal-title":"Calcif. Tissue Int."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1006\/abbi.1998.0720","article-title":"Decorin core protein fragment Leu155-Val260 interacts with TGF-\u03b2 but does not compete for decorin binding to type I collagen","volume":"355","author":"Schonherr","year":"1998","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1016\/0092-8674(92)90627-O","article-title":"Receptors for the TGF-\u03b2 family","volume":"69","author":"Massague","year":"1992","journal-title":"Cell"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1101\/gad.8.2.133","article-title":"The TGF-\u03b2 superfamily: New members, new receptors, and new genetic tests of function in different organisms","volume":"8","author":"Kingsley","year":"1994","journal-title":"Genes Dev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1111\/1348-0421.12344","article-title":"Isoform-specific regulation of transforming growth factor-\u03b2 mRNA expression in macrophages in response to adrenoceptor stimulation","volume":"60","author":"Yanagawa","year":"2016","journal-title":"Microbiol. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1124\/mol.62.1.65","article-title":"Sb-431542 is a potent and specific inhibitor of transforming growth factor-\u03b2 superfamily type I activin receptor-like kinase (ALK) receptors ALK4, ALK5, and ALK7","volume":"62","author":"Inman","year":"2002","journal-title":"Mol. Pharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1124\/mol.62.1.58","article-title":"Inhibition of transforming growth factor (TGF)-\u03b21-induced extracellular matrix with a novel inhibitor of the TGF-\u03b2 type I receptor kinase activity: Sb-431542","volume":"62","author":"Laping","year":"2002","journal-title":"Mol. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1002\/pros.20019","article-title":"In vivo real-time imaging of TGF-\u03b2-induced transcriptional activation of the RANK ligand gene promoter in intraosseous prostate cancer","volume":"59","author":"Zhang","year":"2004","journal-title":"Prostate"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"26217","DOI":"10.1074\/jbc.M111093200","article-title":"Transforming growth factor-\u03b2 induces expression of receptor activator of NF-\u03baB ligand in vascular endothelial cells derived from bone","volume":"277","author":"Ishida","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.mce.2014.10.014","article-title":"Osteoclast formation elicited by interleukin-33 stimulation is dependent upon the type of osteoclast progenitor","volume":"399","author":"Eeles","year":"2015","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.3892\/mmr.2013.1335","article-title":"The role of the serum RANKL\/OPG ratio in the healing of intertrochanteric fractures in elderly patients","volume":"7","author":"Wang","year":"2013","journal-title":"Mol. Med. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1688","DOI":"10.1902\/jop.2006.050352","article-title":"Porcine enamel protein fractions contain transforming growth factor-\u03b21","volume":"77","author":"Nagano","year":"2006","journal-title":"J. Periodontol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.archoralbio.2016.08.024","article-title":"Interleukin-4 released from human gingival fibroblasts reduces osteoclastogenesis","volume":"72","author":"Ujiie","year":"2016","journal-title":"Arch. Oral Biol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/18\/1\/49\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T19:29:23Z","timestamp":1760210963000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/18\/1\/49"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,12,27]]},"references-count":41,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,1]]}},"alternative-id":["ijms18010049"],"URL":"https:\/\/doi.org\/10.3390\/ijms18010049","relation":{"has-preprint":[{"id-type":"doi","id":"10.20944\/preprints201610.0121.v1","asserted-by":"object"}]},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,12,27]]}}}