DC-STAMP Is an Osteoclast Fusogen Engaged in Periodontal Bone Resorption

W Wisitrasameewong, M Kajiya, A Movila, S Rittling, T Ishii, M Suzuki, S Matsuda, Y Mazda, M R Torruella, M M Azuma, K Egashira, M O Freire, H Sasaki, C Y Wang, X Han, M A Taubman, T Kawai

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)685-693
Number of pages9
JournalJournal of Dental Research
Volume96
Issue number6
DOIs
StatePublished - Jun 2017
Externally publishedYes

Fingerprint

Alveolar Bone Loss
Osteoclasts
Bone Resorption
Dendritic Cells
RANK Ligand
Proteins
Ligation
Pasteurella pneumotropica
Periodontitis
Cell Fusion
Bone Marrow Cells
T-Lymphocytes
Injections
Interleukin-1 Receptors
Tumor Necrosis Factor Receptors

Keywords

  • Animals
  • Antibodies, Monoclonal/pharmacology
  • Blotting, Western
  • Bone Resorption/pathology
  • Cell Differentiation
  • Cell Fusion
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression Regulation
  • Male
  • Membrane Proteins/antagonists & inhibitors
  • Mice
  • Mice, Inbred C57BL
  • Nerve Tissue Proteins/antagonists & inhibitors
  • Osteoclasts/drug effects
  • Periodontitis/pathology
  • RANK Ligand/pharmacology
  • Real-Time Polymerase Chain Reaction
  • Signal Transduction

Cite this

Wisitrasameewong, W., Kajiya, M., Movila, A., Rittling, S., Ishii, T., Suzuki, M., ... Kawai, T. (2017). DC-STAMP Is an Osteoclast Fusogen Engaged in Periodontal Bone Resorption. Journal of Dental Research, 96(6), 685-693. https://doi.org/10.1177/0022034517690490

DC-STAMP Is an Osteoclast Fusogen Engaged in Periodontal Bone Resorption. / Wisitrasameewong, W; Kajiya, M; Movila, A; Rittling, S; Ishii, T; Suzuki, M; Matsuda, S; Mazda, Y; Torruella, M R; Azuma, M M; Egashira, K; Freire, M O; Sasaki, H; Wang, C Y; Han, X; Taubman, M A; Kawai, T.

In: Journal of Dental Research, Vol. 96, No. 6, 06.2017, p. 685-693.

Research output: Contribution to journalArticle

Wisitrasameewong, W, Kajiya, M, Movila, A, Rittling, S, Ishii, T, Suzuki, M, Matsuda, S, Mazda, Y, Torruella, MR, Azuma, MM, Egashira, K, Freire, MO, Sasaki, H, Wang, CY, Han, X, Taubman, MA & Kawai, T 2017, 'DC-STAMP Is an Osteoclast Fusogen Engaged in Periodontal Bone Resorption', Journal of Dental Research, vol. 96, no. 6, pp. 685-693. https://doi.org/10.1177/0022034517690490
Wisitrasameewong, W ; Kajiya, M ; Movila, A ; Rittling, S ; Ishii, T ; Suzuki, M ; Matsuda, S ; Mazda, Y ; Torruella, M R ; Azuma, M M ; Egashira, K ; Freire, M O ; Sasaki, H ; Wang, C Y ; Han, X ; Taubman, M A ; Kawai, T. / DC-STAMP Is an Osteoclast Fusogen Engaged in Periodontal Bone Resorption. In: Journal of Dental Research. 2017 ; Vol. 96, No. 6. pp. 685-693.
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abstract = "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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TY - JOUR

T1 - DC-STAMP Is an Osteoclast Fusogen Engaged in Periodontal Bone Resorption

AU - Wisitrasameewong, W

AU - Kajiya, M

AU - Movila, A

AU - Rittling, S

AU - Ishii, T

AU - Suzuki, M

AU - Matsuda, S

AU - Mazda, Y

AU - Torruella, M R

AU - Azuma, M M

AU - Egashira, K

AU - Freire, M O

AU - Sasaki, H

AU - Wang, C Y

AU - Han, X

AU - Taubman, M A

AU - Kawai, T

PY - 2017/6

Y1 - 2017/6

N2 - 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.

AB - 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.

KW - Animals

KW - Antibodies, Monoclonal/pharmacology

KW - Blotting, Western

KW - Bone Resorption/pathology

KW - Cell Differentiation

KW - Cell Fusion

KW - Disease Models, Animal

KW - Enzyme-Linked Immunosorbent Assay

KW - Gene Expression Regulation

KW - Male

KW - Membrane Proteins/antagonists & inhibitors

KW - Mice

KW - Mice, Inbred C57BL

KW - Nerve Tissue Proteins/antagonists & inhibitors

KW - Osteoclasts/drug effects

KW - Periodontitis/pathology

KW - RANK Ligand/pharmacology

KW - Real-Time Polymerase Chain Reaction

KW - Signal Transduction

U2 - 10.1177/0022034517690490

DO - 10.1177/0022034517690490

M3 - Article

C2 - 28199142

VL - 96

SP - 685

EP - 693

JO - Journal of Dental Research

JF - Journal of Dental Research

SN - 0022-0345

IS - 6

ER -