Expression of SOFAT by T- and B-lineage cells may contribute to bone loss

Jarry,Christian R.; Martinez,Elizabeth F.; Peruzzo,Daiane C.; Carregaro,Vanessa; Sacramento,Laís A.; Araújo,Vera C.; Weitzmann,M. Neale; Napimoga,Marcelo H.

doi:10.3892/mmr.2016.5045

Expression of SOFAT by T- and B-lineage cells may contribute to bone loss

Authors:
- Christian R. Jarry
- Elizabeth F. Martinez
- Daiane C. Peruzzo
- Vanessa Carregaro
- Laís A. Sacramento
- Vera C. Araújo
- M. Neale Weitzmann
- Marcelo H. Napimoga
View Affiliations

Affiliations: Periodontal Medicine Research Group, São Leopoldo Mandic Institute and Research Center, Campinas, São Paulo 13045‑755, Brazil, Laboratory of Oral Pathology, São Leopoldo Mandic Institute and Research Center, Campinas, São Paulo 13045‑755, Brazil, Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, São Paulo 14049-900, Brazil, Atlanta Department of Veterans Affairs Medical Center, Decatur, GA 30033, USA, Laboratory of Immunology and Molecular Biology, São Leopoldo Mandic Institute and Research Center, Campinas, São Paulo 13045‑755, Brazil
Published online on: March 24, 2016 https://doi.org/10.3892/mmr.2016.5045
Pages: 4252-4258
Copyright: © Jarry et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

A novel T cell-secreted cytokine, termed secreted osteoclastogenic factor of activated T cells (SOFAT) that induces osteoclastic bone resorption in a RANKL-independent manner, has been described. Our group have previously reported that SOFAT is highly expressed in gingival tissues of patients with chronic periodontitis suggesting a putative role in the bone loss associated with periodontal disease. The aim of the present study was to identify other potential cellular sources of SOFAT in the bone resorptive lesions of patients with periodontal disease. Gingival tissues were biopsied from systemically healthy subjects without periodontal disease (n=5) and patients with chronic periodontitis (n=5), and the presence of SOFAT was analyzed by immunohistochemistry and immunofluorescence staining. The present data demonstrated marked SOFAT staining in diseased periodontal tissues that was predominantly associated with the lymphocytic infiltration of gingival tissues. Notably, in addition to CD3+ T cells, B‑lineage cells including plasma cells also exhibited strong staining for SOFAT. As SOFAT has not previously been reported in B‑lineage cells, splenic T cells and B cells were further purified from BALB/c mice and activated using CD3/CD28 and lipopolysaccharide, respectively. SOFAT was quantified by reverse transcription‑quantitative polymerase chain reaction and was shown to be significantly expressed (P<0.05) in both activated T cells and B cells compared with unstimulated cells. These data support a putative role of SOFAT in the bone loss associated with chronic periodontal disease. In addition, to the best of our knowledge, this study demonstrates for the first time that in addition to T cells, B-lineage cells may also be a significant source of SOFAT in inflammatory states.

View Figures

View References

1	Udagawa N, Takahashi N, Jimi E, Matsuzaki K, Tsurukai T, Itoh K, Nakagawa N, Yasuda H, Goto M and Tsuda E: Osteoblasts/stromal cells stimulate osteoclast activation through expression of osteoclast differentiation factor/RANKL but not macrophage colony-stimulating factor: Receptor activator of NF-kappa B ligand. Bone. 25:517–523. 1999. View Article : Google Scholar : PubMed/NCBI
2	Suda T, Takahashi N, Udagawa N, Jimi E, Gillespie MT and Martin TJ: Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families. Endocr Rev. 20:345–357. 1999. View Article : Google Scholar : PubMed/NCBI
3	Graves DT, Li J and Cochran DL: Inflammation and uncoupling as mechanisms of periodontal bone loss. J Dent Res. 90:143–153. 2011. View Article : Google Scholar :
4	Khalaf H, Lönn J and Bengtsson T: Cytokines and chemokines are differentially expressed in patients with periodontitis: Possible role for TGF-β1 as a marker for disease progression. Cytokine. 67:29–35. 2014. View Article : Google Scholar : PubMed/NCBI
5	Graves DT, Fine D, Teng YT, Van Dyke TE and Hajishengallis G: The use of rodent models to investigate host-bacteria interactions related to periodontal diseases. J Clin Periodontol. 35:89–105. 2008. View Article : Google Scholar : PubMed/NCBI
6	Lacey DL, Timms E, Tan HL, Kelley MJ, Dunstan CR, Burgess T, Elliott R, Colombero A, Elliott G, Scully S, et al: Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell. 93:165–176. 1998. View Article : Google Scholar : PubMed/NCBI
7	Kong YY, Yoshida H, Sarosi I, Tan HL, Timms E, Capparelli C, Morony S, Oliveira-dos-Santos AJ, Van G, Itie A, et al: OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature. 28:315–323. 1999.
8	Teng YT, Nguyen H, Gao X, Kong YY, Gorczynski RM, Singh B, Ellen RP and Penninger JM: Functional human T-cell immunity and osteoprotegerin ligand control alveolar bone destruction in periodontal infection. J Clin Invest. 106:R59–R67. 2000. View Article : Google Scholar : PubMed/NCBI
9	Chen B, Wu W, Sun W, Zhang Q, Yan F and Xiao Y: RANKL expression in periodontal disease: Where does RANKL come from? Biomed Res Int. 2014:7310392014.PubMed/NCBI
10	Seymour GJ and Greenspan JS: The phenotypic characterization of lymphocyte subpopulations in established human periodontal disease. J Periodontal Res. 14:39–46. 1979. View Article : Google Scholar : PubMed/NCBI
11	Taubman MA, Stoufi ED, Ebersole JL and Smith DJ: Phenotypic studies of cells from periodontal disease tissues. J Periodontal Res. 19:587–590. 1984. View Article : Google Scholar : PubMed/NCBI
12	Kajiya M, Giro G, Taubman MA, Han X, Mayer MP and Kawai T: Role of periodontal pathogenic bacteria in RANKL-mediated bone destruction in periodontal disease. J Oral Microbiol. 8:22010.
13	Yun TJ, Chaudhary PM, Shu GL, Frazer JK, Ewings MK, Schwartz SM, Pascual V, Hood LE and Clark EA: OPG/FDCR-1, a TNF receptor family member, is expressed in lymphoid cells and is up-regulated by ligating CD40. J Immunol. 161:6113–6121. 1998.PubMed/NCBI
14	Li Y, Toraldo G, Li A, Yang X, Zhang H, Qian WP and Weitzmann MN: B cells and T cells are critical for the preservation of bone homeostasis and attainment of peak bone mass in vivo. Blood. 109:3839–3848. 2007. View Article : Google Scholar : PubMed/NCBI
15	Weitzmann MN, Cenci S, Rifas L, Haug J, Dipersio J and Pacifici R: T cell activation induces human osteoclast formation via receptor activator of nuclear factor kappaB ligand-dependent and -independent mechanisms. J Bone Miner Res. 16:328–337. 2001. View Article : Google Scholar : PubMed/NCBI
16	Rifas L and Weitzmann MN: A novel T cell cytokine, secreted osteoclastogenic factor of activated T cells, induces osteoclast formation in a RANKL-independent manner. Arthritis Rheum. 60:3324–3335. 2009. View Article : Google Scholar : PubMed/NCBI
17	Jarry CR, Duarte PM, Freitas FF, de Macedo CG, Clemente-Napimoga JT, Saba-Chujfi E, Passador-Santos F, de Araújo VC and Napimoga MH: Secreted osteoclastogenic factor of activated T cells (SOFAT), a novel osteoclast activator, in chronic periodontitis. Hum Immunol. 74:861–866. 2013. View Article : Google Scholar : PubMed/NCBI
18	Armitage GC: Development of a classification system for periodontal diseases and conditions. Ann Periodontol. 4:1–6. 1999. View Article : Google Scholar
19	Araujo MW, Hovey KM, Benedek JR, Grossi SG, Dorn J, Wactawski-Wende J, Genco RJ and Trevisan M: Reproducibility of probing depth measurement using a constant-force electronic probe: Analysis of inter-and intraexaminer variability. J Periodontol. 74:1736–1740. 2003. View Article : Google Scholar
20	Ainamo J and Bay I: Problems and proposals for recording gingivitis and plaque. Int Dent J. 25:229–235. 1975.PubMed/NCBI
21	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar
22	Chen XT, Tan JY, Lei LH and Chen LL: Cytokine levels in plasma and gingival crevicular fluid in chronic periodontitis. Am J Dent. 28:9–12. 2015.PubMed/NCBI
23	Garlet GP: Destructive and protective roles of cytokines in periodontitis: A re-appraisal from host defense and tissue destruction viewpoints. J Dent Res. 89:1349–1363. 2010. View Article : Google Scholar : PubMed/NCBI
24	Rifas L and Avioli LV: A novel T cell cytokine stimulates interleukin-6 in human osteoblastic cells. J Bone Miner Res. 14:1096–1103. 1999. View Article : Google Scholar : PubMed/NCBI
25	Napimoga MH, Demasi AP, Jarry CR, Ortega MC, de Araújo VC and Martinez EF: In vitro evaluation of the biological effect of SOFAT on osteoblasts. Int Immunopharmacol. 26:378–383. 2015. View Article : Google Scholar : PubMed/NCBI
26	Han X, Kawai T, Eastcott JW and Taubman MA: Bacterial-responsive B lymphocytes induce periodontal bone resorption. J Immunol. 176:625–631. 2006. View Article : Google Scholar
27	Kawai T, Matsuyama T, Hosokawa Y, Makihira S, Seki M, Karimbux NY, Goncalves RB, Valverde P, Dibart S, Li YP, et al: B and T lymphocytes are the primary sources of RANKL in the bone resorptive lesion of periodontal disease. Am J Pathol. 169:987–998. 2006. View Article : Google Scholar : PubMed/NCBI