Journal of Molecular Histology

, Volume 44, Issue 3, pp 347–356 | Cite as

Increased PELP1 expression in rat periodontal ligament tissue in response to estrogens treatment

  • Jing Wang
  • Qiang Zhu
  • Shujun Song
  • Jun Dong
  • Lixin Shi
  • Ran Tao
  • Yin Ding
  • Baofa Hong
Original Paper


Estrogens and their receptors are important factors involved in periodontal ligament (PDL) tissue health. As a regulator of estrogen receptors (ER), the proline-, glutamic acid-, and leucine-rich protein 1 (PELP1) may play a role in alveolar bone formation and PDL homeostasis. The aim of the present study was to observe PELP1 expression in rat PDL tissue during estrogen levels manipulations. Twenty-one 8-week old normal female Sprague–Dawley rats were randomly divided into three equal groups: sham-operated controls, ovariectomized (OVX) group, and OVX given 17β-estradiol intraperitoneally (OVX + E2) for 16 weeks. PELP1 expression was down-regulated in the OVX group and was up-regulated in the OVX + E2 group. Periodontal ligament fibroblast cells (PDLFCs) were isolated from PDL tissue, and characterized by immunohistochemical staining. Estradiol treatment of PDLFCs induced PELP1 protein level compared to untreated cells. PELP1 mRNA expression in estradiol-treated cells was relatively low at the beginning of treatment and then steadily increased from hour 4. In conclusion, results indicate that PELP1 is expressed in rat PDL tissue and PDLFCs, and that its expression is up-regulated during estrogen treatment.


Estrogen PELP1 Ovariectomized rats Periodontal ligament 



The authors gratefully acknowledge the support of 306 Hospital of PLA. We thank the staff in the Center of Pathology and Experimental Medicine of 306 Hospital of PLA for their skills, knowledge and advice.

Conflict of interest

No potential conflicts of interest were disclosed.


  1. Abdul-Majeed S et al (2012) Effects of tocotrienol and lovastatin combination on osteoblast and osteoclast activity in estrogen-deficient osteoporosis. Evid Based Complement Alternat Med 2012:960742. doi: 10.1155/2012/960742 PubMedCrossRefGoogle Scholar
  2. Abujazia MA et al (2012) The effects of virgin coconut oil on bone oxidative status in ovariectomised rat. Evid Based Complement Alternat Med 2012:525079. doi: 10.1155/2012/525079 PubMedCrossRefGoogle Scholar
  3. Alegria-Schaffer A et al (2009) Performing and optimizing Western blots with an emphasis on chemiluminescent detection. Methods Enzymol 463:573–599. doi: 10.1016/S0076-6879(09)63033-0 PubMedCrossRefGoogle Scholar
  4. Balasenthil S, Vadlamudi RK (2003) Functional interactions between the estrogen receptor coactivator PELP1/MNAR and retinoblastoma protein. J Biol Chem 278(24):22119–22127. doi: 10.1074/jbc.M212822200M212822200 PubMedCrossRefGoogle Scholar
  5. Barletta F et al (2004) Characterization of the interactions of estrogen receptor and MNAR in the activation of cSrc. Mol Endocrinol 18(5):1096–1108. doi: 10.1210/me.2003-0335me.2003-0335 PubMedCrossRefGoogle Scholar
  6. Bord S et al (2003) The effects of estrogen on osteoprotegerin, RANKL, and estrogen receptor expression in human osteoblasts. Bone 32(2):136–141. doi: 10.1016/S8756-3282(02)00953-5 PubMedCrossRefGoogle Scholar
  7. Brann DW et al (2008) PELP1–a novel estrogen receptor-interacting protein. Mol Cell Endocrinol 290(1–2):2–7. doi: 10.1016/j.mce.2008.04.019 PubMedCrossRefGoogle Scholar
  8. Cao M et al (2007) The expression of estrogen receptors and the effects of estrogen on human periodontal ligament cells. Methods Find Exp Clin Pharmacol 29(5):329–335. doi: 10.1358/mf.2007.29.5.1117560 PubMedCrossRefGoogle Scholar
  9. Cheskis BJ et al (2008) MNAR plays an important role in ERa activation of Src/MAPK and PI3 K/Akt signaling pathways. Steroids 73(9–10):901–905. doi: 10.1016/j.steroids.2007.12.028 PubMedCrossRefGoogle Scholar
  10. Chimutengwende-Gordon M, Khan WS (2011) Advances in the use of stem cells and tissue engineering applications in bone repair. Curr Stem Cell Res Ther 7(2):122–126. doi: BSP/CSCRT/E-Pub/00115 CrossRefGoogle Scholar
  11. DeFriend DJ et al (1994) Investigation of a new pure antiestrogen (ICI 182780) in women with primary breast cancer. Cancer Res 54(2):408–414PubMedGoogle Scholar
  12. Dobrzycka KM et al (2003) Estrogen receptor corepressors—a role in human breast cancer? Endocr Relat Cancer 10(4):517–536PubMedCrossRefGoogle Scholar
  13. Du J et al (2012) The expression pattern of FHL2 during mouse molar development. J Mol Histol 43(3):289–295. doi: 10.1007/s10735-012-9409-z PubMedCrossRefGoogle Scholar
  14. Greger JG et al (2006) Characterization of MNAR expression. Steroids 71(4):317–322. doi: 10.1016/j.steroids.2005.09.016 PubMedCrossRefGoogle Scholar
  15. Grivas PD et al (2009) Expression of ERalpha, ERbeta and co-regulator PELP1/MNAR in colorectal cancer: prognostic significance and clinicopathologic correlations. Cell Oncol 31(3):235–247. doi: 10.3233/CLO-2009-0467 PubMedGoogle Scholar
  16. Hongo H et al (2011) Frontiers in vitamin D; basic research and clinical application. A review on histological findings in bones administered with eldecalcitol. Clin Calcium 21(11):63–70. doi: CliCa111116471654 PubMedGoogle Scholar
  17. Ibi M et al (2007) Establishment of cell lines that exhibit pluripotency from miniature swine periodontal ligaments. Arch Oral Biol 52(10):1002–1008. doi: 10.1016/j.archoralbio.2007.04.009 PubMedCrossRefGoogle Scholar
  18. Isaka J et al (2001) Participation of periodontal ligament cells with regeneration of alveolar bone. J Periodontol 72(3):314–323. doi: 10.1902/jop PubMedCrossRefGoogle Scholar
  19. Jonsson D et al (2011) The human periodontal ligament cell: a fibroblast-like cell acting as an immune cell. J Periodontal Res 46(2):153–157. doi: 10.1111/j.1600-0765.2010.01331.x PubMedCrossRefGoogle Scholar
  20. Kawase T et al (1988) Alkaline phosphatase of human periodontal ligament fibroblast-like cells. Adv Dent Res 2(2):234–239PubMedGoogle Scholar
  21. Liang L et al (2008) Effect of estrogen receptor beta on the osteoblastic differentiation function of human periodontal ligament cells. Arch Oral Biol 53(6):553–557. doi: 10.1016/j.archoralbio.2007.12.011 PubMedCrossRefGoogle Scholar
  22. Liu Y et al (2008) Periodontal ligament stem cell-mediated treatment for periodontitis in miniature swine. Stem Cells 26(4):1065–1073. doi: 10.1634/stemcells.2007-0734 PubMedCrossRefGoogle Scholar
  23. Machtei EE et al (2004) The effect of menstrual cycle on periodontal health. J Periodontol 75(3):408–412. doi: 10.1902 PubMedCrossRefGoogle Scholar
  24. Meyer MR et al (2009) Non-genomic regulation of vascular cell function and growth by estrogen. Mol Cell Endocrinol 308(1–2):9–16. doi: 10.1016/j.mce.2009.03.009 PubMedCrossRefGoogle Scholar
  25. Mishra SK et al (2004) Cloning and functional characterization of PELP1/MNAR promoter. Gene 330:115–122. doi: 10.1016/j.gene.2004.01.011S037811190400037X PubMedCrossRefGoogle Scholar
  26. Nair SS et al (2004) Potential role of a novel transcriptional coactivator PELP1 in histone H1 displacement in cancer cells. Cancer Res 64(18):6416–6423. doi: 10.1158/0008-5472.CAN-04-178664/18/6416 PubMedCrossRefGoogle Scholar
  27. Orwoll ES et al (2009) Sex steroids, periodontal health, and tooth loss in older men. J Dent Res 88(8):704–708. doi: 10.1177/0022034509341013 PubMedCrossRefGoogle Scholar
  28. Pawlak J, Beyer C (2005) Developmental expression of MNAR mRNA in the mouse brain. Cell Tissue Res 320(3):545–549. doi: 10.1007/s00441-005-1090-z PubMedCrossRefGoogle Scholar
  29. Prisby RD et al (2012) Aging and estrogen status: a possible endothelium-dependent vascular coupling mechanism in bone remodeling. PLoS ONE 7(11):e48564. doi: 10.1371/journal.pone.0048564PONE-D-12-23015 PubMedCrossRefGoogle Scholar
  30. Rachon D et al (2008) Effects of black cohosh extract on body weight gain, intra-abdominal fat accumulation, plasma lipids and glucose tolerance in ovariectomized Sprague-Dawley rats. Maturitas 60(3–4):209–215. doi: 10.1016/j.maturitas.2008.06.001 PubMedCrossRefGoogle Scholar
  31. Seo BM et al (2004) Investigation of multipotent postnatal stem cells from human periodontal ligament. Lancet 364(9429):149–155. doi: 10.1016/S0140-6736(04)16627-0S0140673604166270 PubMedCrossRefGoogle Scholar
  32. Sims NA et al (1996) Estradiol treatment transiently increases trabecular bone volume in ovariectomized rats. Bone 19(5):455–461. doi: S8756328296002426 PubMedCrossRefGoogle Scholar
  33. Smuc T et al (2009) Disturbed estrogen and progesterone action in ovarian endometriosis. Mol Cell Endocrinol 301(1–2):59–64. doi: 10.1016/j.mce.2008.07.020 PubMedCrossRefGoogle Scholar
  34. Taichman LS, Eklund SA (2005) Oral contraceptives and periodontal diseases: rethinking the association based upon analysis of National Health and Nutrition Examination Survey data. J Periodontol 76(8):1374–1385. doi: 10.1902 PubMedCrossRefGoogle Scholar
  35. Techawattanawisal W et al (2007) Isolation of multipotent stem cells from adult rat periodontal ligament by neurosphere-forming culture system. Biochem Biophys Res Commun 357(4):917–923. doi: 10.1016/j.bbrc.2007.04.031 PubMedCrossRefGoogle Scholar
  36. Tilakaratne A et al (2000) Effects of hormonal contraceptives on the periodontium, in a population of rural Sri-Lankan women. J Clin Periodontol 27(10):753–757PubMedCrossRefGoogle Scholar
  37. Toran-Allerand CD (2004) Estrogen and the brain: beyond ER-alpha and ER-beta. Exp Gerontol 39(11–12):1579–1586. doi: 10.1016/j.exger.2004.05.006 PubMedCrossRefGoogle Scholar
  38. Vadlamudi RK, Kumar R (2007) Functional and biological properties of the nuclear receptor coregulator PELP1/MNAR. Nucl Recept Signal 5:e004. doi: 10.1621/nrs.05004 PubMedGoogle Scholar
  39. Vadlamudi RK, Wang RA, Mazumdar A et al (2001) Molecular cloning and characterization of PELP1, a novel human coregulator of estrogen receptor alpha. J Biol Chem 276(41):38272–38279. doi: 10.1074/jbc.M103783200M103783200 PubMedGoogle Scholar
  40. Vadlamudi RK et al (2004) Deregulation of estrogen receptor coactivator proline-, glutamic acid-, and leucine-rich protein-1/modulator of nongenomic activity of estrogen receptor in human endometrial tumors. J Clin Endocrinol Metab 89(12):6130–6138. doi: 10.1210/jc.2004-0909 PubMedCrossRefGoogle Scholar
  41. Vadlamudi RK et al (2005) Novel estrogen receptor coactivator PELP1/MNAR gene and ERbeta expression in salivary duct adenocarcinoma: potential therapeutic targets. Hum Pathol 36(6):670–675. doi: 10.1016/j.humpath.2005.03.016 PubMedCrossRefGoogle Scholar
  42. Wang Q et al (2006) Temporal expression of estrogen receptor alpha in rat bone marrow mesenchymal stem cells. Biochem Biophys Res Commun 347(1):117–123. doi: 10.1016/j.bbrc.2006.06.070 PubMedCrossRefGoogle Scholar
  43. Williams MD et al (2007) Differential expression of hormonal and growth factor receptors in salivary duct carcinomas: biologic significance and potential role in therapeutic stratification of patients. Am J Surg Pathol 31(11):1645–1652. doi: 10.1097/PAS.0b013e3180caa09900000478-200711000-00003 PubMedCrossRefGoogle Scholar
  44. Wong CW et al (2002) Estrogen receptor-interacting protein that modulates its nongenomic activity-crosstalk with Src/Erk phosphorylation cascade. Proc Natl Acad Sci USA 99(23):14783–14788. doi: 10.1073/pnas.192569699192569699 PubMedCrossRefGoogle Scholar
  45. Yamaji Y et al (1995) Inflammatory cytokine gene expression in human periodontal ligament fibroblasts stimulated with bacterial lipopolysaccharides. Infect Immun 63(9):3576–3581PubMedGoogle Scholar
  46. Zilli M et al (2009) Molecular mechanisms of endocrine resistance and their implication in the therapy of breast cancer. Biochim Biophys Acta 1795(1):62–81. doi: 10.1016/j.bbcan.2008.08.003 PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  1. 1.Department of Orthodontics, College of StomatologyForth Military Medical UniversityXi’anChina
  2. 2.Department of UrologicalGeneral Hospital of People’s Liberation ArmyBeijingChina
  3. 3.Department of Pathology and Experimental MedicineBeijingChina
  4. 4.Department of Plastic SurgeryGeneral Hospital of People’s Liberation ArmyBeijingChina

Personalised recommendations