DC-STAMP Is an Osteoclast Fusogen Engaged in Periodontal Bone Resorption
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1177/0022034517690490 http://hdl.handle.net/11449/228328 |
Resumo: | Dendritic cell-specific transmembrane protein (DC-STAMP) plays a key role in the induction of osteoclast (OC) cell fusion, as well as DC-mediated immune regulation. While DC-STAMP gene expression is upregulated in the gingival tissue with periodontitis, its pathophysiological roles in periodontitis remain unclear. To evaluate the effects of DC-STAMP in periodontitis, anti-DC-STAMP-monoclonal antibody (mAb) was tested in a mouse model of ligature-induced periodontitis (n = 6-7/group) where Pasteurella pneumotropica (Pp)-reactive immune response activated T cells to produce receptor activator of nuclear factor kappa-B ligand (RANKL), which, in turn, promotes the periodontal bone loss via upregulation of osteoclastogenesis. DC-STAMP was expressed on the cell surface of mature multinuclear OCs, as well as immature mononuclear OCs, in primary cultures of RANKL-stimulated bone marrow cells. Anti-DC-STAMP-mAb suppressed the emergence of large, but not small, multinuclear OCs, suggesting that DC-STAMP is engaged in the late stage of cell fusion. Anti-DC-STAMP-mAb also inhibited pit formation caused by RANKL-stimulated bone marrow cells. Attachment of ligature to a second maxillary molar induced DC-STAMP messenger RNA and protein, along with elevated tartrate-resistant acid phosphatase-positive (TRAP+) OCs and alveolar bone loss. As we expected, systemic administration of anti-DC-STAMP-mAb downregulated the ligature-induced alveolar bone loss. Importantly, local injection of anti-DC-STAMP-mAb also suppressed alveolar bone loss and reduced the total number of multinucleated TRAP+ cells in mice that received ligature attachment. Attachment of ligature induced significantly elevated tumor necrosis factor-α, interleukin-1β, and RANKL in the gingival tissue compared with the control site without ligature (P < 0.05), which was unaffected by local injection with either anti-DC-STAMP-mAb or control-mAb. Neither in vivo anti-Pp IgG antibody nor in vitro anti-Pp T-cell response and resultant production of RANKL was affected by anti-DC-STAMP-mAb. This study illustrated the roles of DC-STAMP in promoting local OC cell fusion without affecting adaptive immune responses to oral bacteria. Therefore, it is plausible that a novel therapeutic regimen targeting DC-STAMP could suppress periodontal bone loss. |
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DC-STAMP Is an Osteoclast Fusogen Engaged in Periodontal Bone Resorptionbone resorptioncell fusionimmunitymiceosteoclastsperiodontal disease(s)/periodontitisDendritic cell-specific transmembrane protein (DC-STAMP) plays a key role in the induction of osteoclast (OC) cell fusion, as well as DC-mediated immune regulation. While DC-STAMP gene expression is upregulated in the gingival tissue with periodontitis, its pathophysiological roles in periodontitis remain unclear. To evaluate the effects of DC-STAMP in periodontitis, anti-DC-STAMP-monoclonal antibody (mAb) was tested in a mouse model of ligature-induced periodontitis (n = 6-7/group) where Pasteurella pneumotropica (Pp)-reactive immune response activated T cells to produce receptor activator of nuclear factor kappa-B ligand (RANKL), which, in turn, promotes the periodontal bone loss via upregulation of osteoclastogenesis. DC-STAMP was expressed on the cell surface of mature multinuclear OCs, as well as immature mononuclear OCs, in primary cultures of RANKL-stimulated bone marrow cells. Anti-DC-STAMP-mAb suppressed the emergence of large, but not small, multinuclear OCs, suggesting that DC-STAMP is engaged in the late stage of cell fusion. Anti-DC-STAMP-mAb also inhibited pit formation caused by RANKL-stimulated bone marrow cells. Attachment of ligature to a second maxillary molar induced DC-STAMP messenger RNA and protein, along with elevated tartrate-resistant acid phosphatase-positive (TRAP+) OCs and alveolar bone loss. As we expected, systemic administration of anti-DC-STAMP-mAb downregulated the ligature-induced alveolar bone loss. Importantly, local injection of anti-DC-STAMP-mAb also suppressed alveolar bone loss and reduced the total number of multinucleated TRAP+ cells in mice that received ligature attachment. Attachment of ligature induced significantly elevated tumor necrosis factor-α, interleukin-1β, and RANKL in the gingival tissue compared with the control site without ligature (P < 0.05), which was unaffected by local injection with either anti-DC-STAMP-mAb or control-mAb. Neither in vivo anti-Pp IgG antibody nor in vitro anti-Pp T-cell response and resultant production of RANKL was affected by anti-DC-STAMP-mAb. This study illustrated the roles of DC-STAMP in promoting local OC cell fusion without affecting adaptive immune responses to oral bacteria. Therefore, it is plausible that a novel therapeutic regimen targeting DC-STAMP could suppress periodontal bone loss.Department of Periodontology Faculty of Dentistry Chulalongkorn UniversityDepartment of Immunology and Infectious Diseases Forsyth InstituteHarvard School of Dental MedicineHiroshima University Graduate School of Biomedical Sciences Periodontal MedicineTokyo Dental CollegeCollege of Dentistry Ohio State UniversityAraçatuba Dental School Department of Endodontics UnivEstadual PaulistaLION Corporation Research and Development HeadquartersUCLA Lab of Molecular Signaling Division of Oral Biology and Medicine UCLADepartment of Periodontology NOVA Southeastern University College of Dental Medicine, 3200 South University DriveAraçatuba Dental School Department of Endodontics UnivEstadual PaulistaChulalongkorn UniversityForsyth InstituteHarvard School of Dental MedicinePeriodontal MedicineTokyo Dental CollegeOhio State UniversityUniversidade Estadual Paulista (UNESP)Research and Development HeadquartersUCLACollege of Dental MedicineWisitrasameewong, W.Kajiya, M.Movila, A.Rittling, S. [UNESP]Ishii, T.Suzuki, M.Matsuda, S.Mazda, Y.Torruella, M. R.Azuma, M. M. [UNESP]Egashira, K.Freire, M. O.Sasaki, H.Wang, C. Y.Han, X.Taubman, M. A.Kawai, T.2022-04-29T08:03:58Z2022-04-29T08:03:58Z2017-06-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article685-693http://dx.doi.org/10.1177/0022034517690490Journal of Dental Research, v. 96, n. 6, p. 685-693, 2017.1544-05910022-0345http://hdl.handle.net/11449/22832810.1177/00220345176904902-s2.0-85019571966Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengJournal of Dental Researchinfo:eu-repo/semantics/openAccess2022-04-29T08:03:59Zoai:repositorio.unesp.br:11449/228328Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462022-04-29T08:03:59Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
DC-STAMP Is an Osteoclast Fusogen Engaged in Periodontal Bone Resorption |
title |
DC-STAMP Is an Osteoclast Fusogen Engaged in Periodontal Bone Resorption |
spellingShingle |
DC-STAMP Is an Osteoclast Fusogen Engaged in Periodontal Bone Resorption Wisitrasameewong, W. bone resorption cell fusion immunity mice osteoclasts periodontal disease(s)/periodontitis |
title_short |
DC-STAMP Is an Osteoclast Fusogen Engaged in Periodontal Bone Resorption |
title_full |
DC-STAMP Is an Osteoclast Fusogen Engaged in Periodontal Bone Resorption |
title_fullStr |
DC-STAMP Is an Osteoclast Fusogen Engaged in Periodontal Bone Resorption |
title_full_unstemmed |
DC-STAMP Is an Osteoclast Fusogen Engaged in Periodontal Bone Resorption |
title_sort |
DC-STAMP Is an Osteoclast Fusogen Engaged in Periodontal Bone Resorption |
author |
Wisitrasameewong, W. |
author_facet |
Wisitrasameewong, W. Kajiya, M. Movila, A. Rittling, S. [UNESP] Ishii, T. Suzuki, M. Matsuda, S. Mazda, Y. Torruella, M. R. Azuma, M. M. [UNESP] Egashira, K. Freire, M. O. Sasaki, H. Wang, C. Y. Han, X. Taubman, M. A. Kawai, T. |
author_role |
author |
author2 |
Kajiya, M. Movila, A. Rittling, S. [UNESP] Ishii, T. Suzuki, M. Matsuda, S. Mazda, Y. Torruella, M. R. Azuma, M. M. [UNESP] Egashira, K. Freire, M. O. Sasaki, H. Wang, C. Y. Han, X. Taubman, M. A. Kawai, T. |
author2_role |
author author author author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Chulalongkorn University Forsyth Institute Harvard School of Dental Medicine Periodontal Medicine Tokyo Dental College Ohio State University Universidade Estadual Paulista (UNESP) Research and Development Headquarters UCLA College of Dental Medicine |
dc.contributor.author.fl_str_mv |
Wisitrasameewong, W. Kajiya, M. Movila, A. Rittling, S. [UNESP] Ishii, T. Suzuki, M. Matsuda, S. Mazda, Y. Torruella, M. R. Azuma, M. M. [UNESP] Egashira, K. Freire, M. O. Sasaki, H. Wang, C. Y. Han, X. Taubman, M. A. Kawai, T. |
dc.subject.por.fl_str_mv |
bone resorption cell fusion immunity mice osteoclasts periodontal disease(s)/periodontitis |
topic |
bone resorption cell fusion immunity mice osteoclasts periodontal disease(s)/periodontitis |
description |
Dendritic cell-specific transmembrane protein (DC-STAMP) plays a key role in the induction of osteoclast (OC) cell fusion, as well as DC-mediated immune regulation. While DC-STAMP gene expression is upregulated in the gingival tissue with periodontitis, its pathophysiological roles in periodontitis remain unclear. To evaluate the effects of DC-STAMP in periodontitis, anti-DC-STAMP-monoclonal antibody (mAb) was tested in a mouse model of ligature-induced periodontitis (n = 6-7/group) where Pasteurella pneumotropica (Pp)-reactive immune response activated T cells to produce receptor activator of nuclear factor kappa-B ligand (RANKL), which, in turn, promotes the periodontal bone loss via upregulation of osteoclastogenesis. DC-STAMP was expressed on the cell surface of mature multinuclear OCs, as well as immature mononuclear OCs, in primary cultures of RANKL-stimulated bone marrow cells. Anti-DC-STAMP-mAb suppressed the emergence of large, but not small, multinuclear OCs, suggesting that DC-STAMP is engaged in the late stage of cell fusion. Anti-DC-STAMP-mAb also inhibited pit formation caused by RANKL-stimulated bone marrow cells. Attachment of ligature to a second maxillary molar induced DC-STAMP messenger RNA and protein, along with elevated tartrate-resistant acid phosphatase-positive (TRAP+) OCs and alveolar bone loss. As we expected, systemic administration of anti-DC-STAMP-mAb downregulated the ligature-induced alveolar bone loss. Importantly, local injection of anti-DC-STAMP-mAb also suppressed alveolar bone loss and reduced the total number of multinucleated TRAP+ cells in mice that received ligature attachment. Attachment of ligature induced significantly elevated tumor necrosis factor-α, interleukin-1β, and RANKL in the gingival tissue compared with the control site without ligature (P < 0.05), which was unaffected by local injection with either anti-DC-STAMP-mAb or control-mAb. Neither in vivo anti-Pp IgG antibody nor in vitro anti-Pp T-cell response and resultant production of RANKL was affected by anti-DC-STAMP-mAb. This study illustrated the roles of DC-STAMP in promoting local OC cell fusion without affecting adaptive immune responses to oral bacteria. Therefore, it is plausible that a novel therapeutic regimen targeting DC-STAMP could suppress periodontal bone loss. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-06-01 2022-04-29T08:03:58Z 2022-04-29T08:03:58Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1177/0022034517690490 Journal of Dental Research, v. 96, n. 6, p. 685-693, 2017. 1544-0591 0022-0345 http://hdl.handle.net/11449/228328 10.1177/0022034517690490 2-s2.0-85019571966 |
url |
http://dx.doi.org/10.1177/0022034517690490 http://hdl.handle.net/11449/228328 |
identifier_str_mv |
Journal of Dental Research, v. 96, n. 6, p. 685-693, 2017. 1544-0591 0022-0345 10.1177/0022034517690490 2-s2.0-85019571966 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Journal of Dental Research |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
685-693 |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
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1799964441271336960 |