Generation of a T lymphocyte-specific protease-activated receptor-2 null mouse for investigation of periodontal disease-induced bone loss

Nidhish Francis, Charles Pagel, Neil O'Brien-Simpson, Rob Pike, Eleanor Mackie

Research output: Other contribution to conferencePoster

Abstract

Periodontal diseases are characterised by gingival inflammation and alveolar bone loss. A major etiological agent is Porphyromonas gingivalis, which secretes proteases capable of activating protease-activated receptor-2 (PAR2). Our
laboratory has previously demonstrated that when subjected to an established P.gingivalis-induced periodontitis model PAR2 global knockout mice display an impaired immune response and reduced bone loss. Hence, we hypothesised that
PAR2 expressed on T-cells is required for the establishment and progression of periodontal disease. To test this hypothesis, CD4+ T-cells were adoptively transferred from PAR2+/+ or global PAR2-/-mice into αβ T-cell receptor
knockout mice. Following the adoptive transfer, the mice were subjected to an established P.gingivalis-induced periodontitis model. Significant alveolar bone loss was observed in αβ T-cell receptor knockout mice that received Tcells
from PAR2 +/+ mice, but not in αβ T-cell receptor knockout mice that received T-cells from PAR2-/- mice, suggesting that PAR2 expression by T-cells is pivotal in P. gingivalis induced bone loss. In order to further test the role
of PAR2 on T-cells and other cell types we have generated mice harbouring floxed PAR2 alleles. These mice have been bred with lymphocyte protein tyrosine kinase (Lck)-Cre transgenic mice to produce mice in which PAR2 is deleted in Tcells during the DN3 stage of differentiation. The efficiency of PAR2 deletion was determined in T-cells isolated from various lymphoid tissues including spleen, thymus and lymph nodes. We observed a 94% and 40% deletion of the PAR2 gene in the T-cells isolated from thymus and spleen respectively, suggesting a previously unidentified role for PAR2 during β-selection in the early stages of T-cell maturation. The findings of this project will help us better understand the specific role of PAR2 and T-cells in mediating the bone loss associated with periodontitis and help in designing novel therapies with which to treat the disease.
Original languageEnglish
Pages57-58
Publication statusPublished - 2014
Event24th Australia and New Zealand Bone Mineral Society (ANZBMS) Annual Scientific Meeting - Millennium Hotel, Queenstown, New Zealand
Duration: 07 Sep 201410 Sep 2014
https://www.anzbms.org.au/documents/ANZBMSASM2014Handbook1.pdf (conference handbook)

Conference

Conference24th Australia and New Zealand Bone Mineral Society (ANZBMS) Annual Scientific Meeting
CountryNew Zealand
CityQueenstown
Period07/09/1410/09/14
Internet address

Fingerprint

PAR-2 Receptor
Periodontal Diseases
T-Lymphocytes
Bone and Bones
Periodontitis
Knockout Mice
Alveolar Bone Loss
Porphyromonas gingivalis
T-Cell Antigen Receptor
Thymus Gland
Spleen
Adoptive Transfer
Lymphoid Tissue

Cite this

Francis, N., Pagel, C., O'Brien-Simpson, N., Pike, R., & Mackie, E. (2014). Generation of a T lymphocyte-specific protease-activated receptor-2 null mouse for investigation of periodontal disease-induced bone loss. 57-58. Poster session presented at 24th Australia and New Zealand Bone Mineral Society (ANZBMS) Annual Scientific Meeting, Queenstown, New Zealand.
Francis, Nidhish ; Pagel, Charles ; O'Brien-Simpson, Neil ; Pike, Rob ; Mackie, Eleanor. / Generation of a T lymphocyte-specific protease-activated receptor-2 null mouse for investigation of periodontal disease-induced bone loss. Poster session presented at 24th Australia and New Zealand Bone Mineral Society (ANZBMS) Annual Scientific Meeting, Queenstown, New Zealand.
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Francis, N, Pagel, C, O'Brien-Simpson, N, Pike, R & Mackie, E 2014, 'Generation of a T lymphocyte-specific protease-activated receptor-2 null mouse for investigation of periodontal disease-induced bone loss' 24th Australia and New Zealand Bone Mineral Society (ANZBMS) Annual Scientific Meeting, Queenstown, New Zealand, 07/09/14 - 10/09/14, pp. 57-58.

Generation of a T lymphocyte-specific protease-activated receptor-2 null mouse for investigation of periodontal disease-induced bone loss. / Francis, Nidhish; Pagel, Charles; O'Brien-Simpson, Neil; Pike, Rob; Mackie, Eleanor.

2014. 57-58 Poster session presented at 24th Australia and New Zealand Bone Mineral Society (ANZBMS) Annual Scientific Meeting, Queenstown, New Zealand.

Research output: Other contribution to conferencePoster

TY - CONF

T1 - Generation of a T lymphocyte-specific protease-activated receptor-2 null mouse for investigation of periodontal disease-induced bone loss

AU - Francis, Nidhish

AU - Pagel, Charles

AU - O'Brien-Simpson, Neil

AU - Pike, Rob

AU - Mackie, Eleanor

PY - 2014

Y1 - 2014

N2 - Periodontal diseases are characterised by gingival inflammation and alveolar bone loss. A major etiological agent is Porphyromonas gingivalis, which secretes proteases capable of activating protease-activated receptor-2 (PAR2). Ourlaboratory has previously demonstrated that when subjected to an established P.gingivalis-induced periodontitis model PAR2 global knockout mice display an impaired immune response and reduced bone loss. Hence, we hypothesised thatPAR2 expressed on T-cells is required for the establishment and progression of periodontal disease. To test this hypothesis, CD4+ T-cells were adoptively transferred from PAR2+/+ or global PAR2-/-mice into αβ T-cell receptorknockout mice. Following the adoptive transfer, the mice were subjected to an established P.gingivalis-induced periodontitis model. Significant alveolar bone loss was observed in αβ T-cell receptor knockout mice that received Tcellsfrom PAR2 +/+ mice, but not in αβ T-cell receptor knockout mice that received T-cells from PAR2-/- mice, suggesting that PAR2 expression by T-cells is pivotal in P. gingivalis induced bone loss. In order to further test the roleof PAR2 on T-cells and other cell types we have generated mice harbouring floxed PAR2 alleles. These mice have been bred with lymphocyte protein tyrosine kinase (Lck)-Cre transgenic mice to produce mice in which PAR2 is deleted in Tcells during the DN3 stage of differentiation. The efficiency of PAR2 deletion was determined in T-cells isolated from various lymphoid tissues including spleen, thymus and lymph nodes. We observed a 94% and 40% deletion of the PAR2 gene in the T-cells isolated from thymus and spleen respectively, suggesting a previously unidentified role for PAR2 during β-selection in the early stages of T-cell maturation. The findings of this project will help us better understand the specific role of PAR2 and T-cells in mediating the bone loss associated with periodontitis and help in designing novel therapies with which to treat the disease.

AB - Periodontal diseases are characterised by gingival inflammation and alveolar bone loss. A major etiological agent is Porphyromonas gingivalis, which secretes proteases capable of activating protease-activated receptor-2 (PAR2). Ourlaboratory has previously demonstrated that when subjected to an established P.gingivalis-induced periodontitis model PAR2 global knockout mice display an impaired immune response and reduced bone loss. Hence, we hypothesised thatPAR2 expressed on T-cells is required for the establishment and progression of periodontal disease. To test this hypothesis, CD4+ T-cells were adoptively transferred from PAR2+/+ or global PAR2-/-mice into αβ T-cell receptorknockout mice. Following the adoptive transfer, the mice were subjected to an established P.gingivalis-induced periodontitis model. Significant alveolar bone loss was observed in αβ T-cell receptor knockout mice that received Tcellsfrom PAR2 +/+ mice, but not in αβ T-cell receptor knockout mice that received T-cells from PAR2-/- mice, suggesting that PAR2 expression by T-cells is pivotal in P. gingivalis induced bone loss. In order to further test the roleof PAR2 on T-cells and other cell types we have generated mice harbouring floxed PAR2 alleles. These mice have been bred with lymphocyte protein tyrosine kinase (Lck)-Cre transgenic mice to produce mice in which PAR2 is deleted in Tcells during the DN3 stage of differentiation. The efficiency of PAR2 deletion was determined in T-cells isolated from various lymphoid tissues including spleen, thymus and lymph nodes. We observed a 94% and 40% deletion of the PAR2 gene in the T-cells isolated from thymus and spleen respectively, suggesting a previously unidentified role for PAR2 during β-selection in the early stages of T-cell maturation. The findings of this project will help us better understand the specific role of PAR2 and T-cells in mediating the bone loss associated with periodontitis and help in designing novel therapies with which to treat the disease.

M3 - Poster

SP - 57

EP - 58

ER -

Francis N, Pagel C, O'Brien-Simpson N, Pike R, Mackie E. Generation of a T lymphocyte-specific protease-activated receptor-2 null mouse for investigation of periodontal disease-induced bone loss. 2014. Poster session presented at 24th Australia and New Zealand Bone Mineral Society (ANZBMS) Annual Scientific Meeting, Queenstown, New Zealand.