Estrogen enhances the bone regeneration potential of periodontal ligament stem cells derived from osteoporotic rats and seeded on nano-hydroxyapatite/collagen/poly(L-lactide)

E,Ling-Ling; Xu,Wen-Huan; Feng,Lin; Liu,Yi; Cai,Dong-Qing; Wen,Ning; Zheng,Wen-Jie

doi:10.3892/ijmm.2016.2559

Estrogen enhances the bone regeneration potential of periodontal ligament stem cells derived from osteoporotic rats and seeded on nano-hydroxyapatite/collagen/poly(L-lactide)

Authors:
- Ling-Ling E
- Wen-Huan Xu
- Lin Feng
- Yi Liu
- Dong-Qing Cai
- Ning Wen
- Wen-Jie Zheng
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Affiliations: Institute of Stomatology, Chinese PLA General Hospital, Beijing 100853, P.R. China, Scientific Research Department, Medical Administrative Division, Chinese PLA General Hospital, Beijing 100853, P.R. China, Department of Chemistry, Jinan University, Guangzhou, Guangdong 510632, P.R. China
Published online on: April 12, 2016 https://doi.org/10.3892/ijmm.2016.2559
Pages: 1475-1486
Copyright: © E et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

This study investigated the effects of estrogen on the bone regeneration potential of periodontal ligament stem cells (PDLSCs) derived from osteoporotic rats and seeded on a collagen-based composite scaffold [nano-hydroxyapatite/collagen/poly(L-lactide) (nHAC/PLA)]. For this purpose, 48 healthy 3‑month-old Sprague-Dawley female rats were divided into 2 groups as follows: the bilaterally ovariectomized (OVX) rats and sham‑operated rats. The PDLSCs were isolated at 3 months after surgery (by which time postmenopausal osteoporosis had developed). The effects of estrogen on the characteristics of these cells seeded in a culture plate and of the cells seeded on nHAC/PLA were then investigated. The PDLSC + nHAC/PLA constructs were implanted subcutaneously into the backs of severe combined immunodeficient (SCID) mice for 12 weeks in order to examine the role of estrogen in the bone formation ability of PDLSCs derived from osteoporotic rats. The results from methyl thiazolyl tetrazolium (MTT) assay revealed that the proliferation of the cells derived from the rats in the OVX group was significantly higher than that of the cells derived from the rats in the sham-operated group at the stage of logarithmic growth. The staining intensity of alkaline phosphatase (ALP) and the mineralization of the cells derived from the rats in the OVX group was significantly weaker than that of the cells from the rats in the sham-operated group. When the PDLSCs were seeded on nHAC/PLA, ALP activity, osteocalcin (OCN) secretion, mineral formation and the mRNA expression levels of ALP, OCN, estrogen receptor (ER)α and ERβ in the cells derived from the rats in the OVX group were markedly decreased. Treatment with 17β-estradiol (E2) significantly weakened the proliferative ability of the cells derived from the OVX group rats, and enhanced their osteogenic differentiation ability and the mRNA expression levels of ALP, OCN, ERα and ERβ. When the constructs were implanted into the backs of SCID mice for 12 weeks, the results of histological analysis indicated that the constructs derived from the OVX group rats had a few newly formed bones and osteoids; however, a great number of newly formed bones and osteoids were present in the ones from the sham-operated group and the OVX + E2 group rats. Our findings further indicate that estrogen deficiency impairs the osteogenic differentiation potential of PDLSCs, and that ER plays an important role in the bone regeneration ability of PDLSCs. Estrogen enhances the bone regeneration potential of PDLSCs derived from osteoporotic rats and seeded on nHAC/PLA. This study may provide insight into the clinical management of periodontal bone tissue repair in postmenopausal women with the use of estrogen-mediated PDLSCs seeded on nHAC/PLA.

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1	Bertonazzi A, Nelson B, Salvador J and Umland E: The smallest available estradiol transdermal patch: a new treatment option for the prevention of postmenopausal osteoporosis. Womens Health (Lond Engl). 11:815–824. 2015. View Article : Google Scholar
2	Daniell HW: Postmenopausal tooth loss. Contributions to edentulism by osteoporosis and cigarette smoking. Arch Intern Med. 143:1678–1682. 1983. View Article : Google Scholar : PubMed/NCBI
3	Tominari T, Hirata M, Matsumoto C, Inada M and Miyaura C: Polymethoxy flavonoids, nobiletin and tangeretin, prevent lipopolysaccharide-induced inflammatory bone loss in an experimental model for periodontitis. J Pharmacol Sci. 119:390–394. 2012. View Article : Google Scholar : PubMed/NCBI
4	Kobayashi M, Matsumoto C, Hirata M, Tominari T, Inada M and Miyaura C: The correlation between postmenopausal osteoporosis and inflammatory periodontitis regarding bone loss in experimental models. Exp Anim. 61:183–187. 2012. View Article : Google Scholar : PubMed/NCBI
5	Marques MR, da Silva MA, Manzi FR, Cesar-Neto JB, Nociti FH Jr and Barros SP: Effect of intermittent PTH administration in the periodontitis-associated bone loss in ovariectomized rats. Arch Oral Biol. 50:421–429. 2005. View Article : Google Scholar : PubMed/NCBI
6	Duarte PM, de Assis DR, Casati MZ, Sallum AW, Sallum EA and Nociti FH Jr: Alendronate may protect against increased periodontitis-related bone loss in estrogen-deficient rats. J Periodontol. 75:1196–1202. 2004. View Article : Google Scholar : PubMed/NCBI
7	Reinhardt RA, Payne JB, Maze CA, Patil KD, Gallagher SJ and Mattson JS: Influence of estrogen and osteopenia/osteoporosis on clinical periodontitis in postmenopausal women. J Periodontol. 70:823–828. 1999. View Article : Google Scholar : PubMed/NCBI
8	Palomo L, Chitguppi R, Buencamino MC, Santos D and Thacker H: A need to educate postmenopausal women of their periodontal health. J Indian Soc Periodontol. 17:225–227. 2013. View Article : Google Scholar : PubMed/NCBI
9	Pepelassi E, Nicopoulou-Karayianni K, Archontopoulou AD, Mitsea A, Kavadella A, Tsiklakis K, Vrotsos I, Devlin H and Horner K: The relationship between osteoporosis and periodontitis in women aged 45–70 years. Oral Dis. 18:353–359. 2012. View Article : Google Scholar
10	Haas AN, Rösing CK, Oppermann RV, Albandar JM and Susin C: Association among menopause, hormone replacement therapy, and periodontal attachment loss in southern Brazilian women. J Periodontol. 80:1380–1387. 2009. View Article : Google Scholar : PubMed/NCBI
11	Lerner UH: Inflammation-induced bone remodeling in periodontal disease and the influence of post-menopausal osteoporosis. J Dent Res. 85:596–607. 2006. View Article : Google Scholar : PubMed/NCBI
12	Taguchi A, Tanimoto K, Suei Y, Otani K and Wada T: Oral signs as indicators of possible osteoporosis in elderly women. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 80:612–616. 1995. View Article : Google Scholar : PubMed/NCBI
13	Klemetti E: A review of residual ridge resorption and bone density. J Prosthet Dent. 75:512–514. 1996. View Article : Google Scholar : PubMed/NCBI
14	Hirai T, Ishijima T, Hashikawa Y and Yajima T: Osteoporosis and reduction of residual ridge in edentulous patients. J Prosthet Dent. 69:49–56. 1993. View Article : Google Scholar : PubMed/NCBI
15	von Wowern N and Kollerup G: Symptomatic osteoporosis: A risk factor for residual ridge reduction of the jaws. J Prosthet Dent. 67:656–660. 1992. View Article : Google Scholar : PubMed/NCBI
16	Gonçalves PF, Gurgel BC, Pimentel SP, Sallum EA, Sallum AW, Casati MZ and Nociti FH Jr: Effect of two different approaches for root decontamination on new cementum formation following guided tissue regeneration: A histomorphometric study in dogs. J Periodontal Res. 41:535–540. 2006. View Article : Google Scholar : PubMed/NCBI
17	Hoffmann T, Richter S, Meyle J, Gonzales JR, Heinz B, Arjomand M, Sculean A, Reich E, Jepsen K, Jepsen S and Boedeker RH: A randomized clinical multicentre trial comparing enamel matrix derivative and membrane treatment of buccal class II furcation involvement in mandibular molars. Part III: Patient factors and treatment outcome. J Clin Periodontol. 33:575–583. 2006. View Article : Google Scholar : PubMed/NCBI
18	Needleman IG, Worthington HV, Giedrys-Leeper E and Tucker RJ: Guided tissue regeneration for periodontal infra-bony defects. Cochrane Database Syst Rev. Apr 19–2006.Epub ahead of print. CD001724PubMed/NCBI
19	Venezia E, Goldstein M, Boyan BD and Schwartz Z: The use of enamel matrix derivative in the treatment of periodontal defects: A literature review and meta-analysis. Crit Rev Oral Biol Med. 15:382–402. 2004. View Article : Google Scholar : PubMed/NCBI
20	Kaigler D, Cirelli JA and Giannobile WV: Growth factor delivery for oral and periodontal tissue engineering. Expert Opin Drug Deliv. 3:647–662. 2006. View Article : Google Scholar : PubMed/NCBI
21	Blumenthal NM: A clinical comparison of collagen membranes with e-PTFE membranes in the treatment of human mandibular buccal class II furcation defects. J Periodontol. 64:925–933. 1993. View Article : Google Scholar : PubMed/NCBI
22	Liu Y, Zheng Y, Ding G, Fang D, Zhang C, Bartold PM, Gronthos S, Shi S and Wang S: Periodontal ligament stem cell-mediated treatment for periodontitis in miniature swine. Stem Cells. 26:1065–1073. 2008. View Article : Google Scholar : PubMed/NCBI
23	Seo BM, Miura M, Gronthos S, Bartold PM, Batouli S, Brahim J, Young M, Robey PG, Wang CY and Shi S: Investigation of multi-potent postnatal stem cells from human periodontal ligament. Lancet. 364:149–155. 2004. View Article : Google Scholar : PubMed/NCBI
24	Zhu M, Kohan E, Bradley J, Hedrick M, Benhaim P and Zuk P: The effect of age on osteogenic, adipogenic and proliferative potential of female adipose-derived stem cells. J Tissue Eng Regen Med. 3:290–301. 2009. View Article : Google Scholar : PubMed/NCBI
25	Aldahmash A, Zaher W, Al-Nbaheen M and Kassem M: Human stromal (mesenchymal) stem cells: Basic biology and current clinical use for tissue regeneration. Ann Saudi Med. 32:68–77. 2012.
26	Chen FP, Hu CH and Wang KC: Estrogen modulates osteogenic activity and estrogen receptor mRNA in mesenchymal stem cells of women. Climacteric. 16:154–160. 2013. View Article : Google Scholar
27	Morishita M, Yamamura T, Bachchu MA, Shimazu A and Iwamoto Y: The effects of oestrogen on osteocalcin production by human periodontal ligament cells. Arch Oral Biol. 43:329–333. 1998. View Article : Google Scholar : PubMed/NCBI
28	Morishita M, Yamamura T, Shimazu A, Bachchu AH and Iwamoto Y: Estradiol enhances the production of mineralized nodules by human periodontal ligament cells. J Clin Periodontol. 26:748–751. 1999. View Article : Google Scholar : PubMed/NCBI
29	Mamalis A, Markopoulou C, Lagou A and Vrotsos I: Oestrogen regulates proliferation, osteoblastic differentiation, collagen synthesis and periostin gene expression in human periodontal ligament cells through oestrogen receptor beta. Arch Oral Biol. 56:446–455. 2011. View Article : Google Scholar
30	Liang L, Yu JF, Wang Y, Wang G and Ding Y: Effect of estrogen receptor beta on the osteoblastic differentiation function of human periodontal ligament cells. Arch Oral Biol. 53:553–557. 2008. View Article : Google Scholar : PubMed/NCBI
31	Cao M, Shu L, Li J, Su J, Zhang W, Wang Q, Guo T and Ding Y: The expression of estrogen receptors and the effects of estrogen on human periodontal ligament cells. Methods Find Exp Clin Pharmacol. 29:329–335. 2007. View Article : Google Scholar : PubMed/NCBI
32	Zhang B, Li Y, Zhou Q and Ding Y: Estrogen deficiency leads to impaired osteogenic differentiation of periodontal ligament stem cells in rats. Tohoku J Exp Med. 223:177–186. 2011. View Article : Google Scholar : PubMed/NCBI
33	Liao S, Wang W, Uo M, Ohkawa S, Akasaka T, Tamura K, Cui F and Watari F: A three-layered nano-carbonated hydroxyapatite/collagen/PLGA composite membrane for guided tissue regeneration. Biomaterials. 26:7564–7571. 2005. View Article : Google Scholar : PubMed/NCBI
34	Liu HC, e LL, Wang DS, Su F, Wu X, Shi ZP, Lv Y and Wang JZ: Reconstruction of alveolar bone defects using bone morphogenetic protein 2 mediated rabbit dental pulp stem cells seeded on nano-hydroxyapatite/collagen/poly(L-lactide). Tissue Eng Part A. 17:2417–2433. 2011. View Article : Google Scholar : PubMed/NCBI
35	Yu SJ, Liu HC, Ling-Ling E, Wang DS and Zhu GX: Proliferation and differentiation of osteoblasts from the mandible of osteoporotic rats. Exp Biol Med (Maywood). 237:395–406. 2012. View Article : Google Scholar
36	Gay IC, Chen S and MacDougall M: Isolation and characterization of multipotent human periodontal ligament stem cells. Orthod Craniofac Res. 10:149–160. 2007. View Article : Google Scholar : PubMed/NCBI
37	Zheng W, Wang S, Ma D, Tang L, Duan Y and Jin Y: Loss of proliferation and differentiation capacity of aged human periodontal ligament stem cells and rejuvenation by exposure to the young extrinsic environment. Tissue Eng Part A. 15:2363–2371. 2009. View Article : Google Scholar : PubMed/NCBI
38	E LL, Xu LL, Wu X, Wang DS, Lv Y, Wang JZ and Liu HC: The interactions between rat-adipose-derived stromal cells, recombinant human bone morphogenetic protein-2, and beta-tricalcium phosphate play an important role in bone tissue engineering. Tissue Eng Part A. 16:2927–2940. 2010. View Article : Google Scholar : PubMed/NCBI
39	Barrilleaux B, Phinney DG, Prockop DJ and O'Connor KC: Review: Ex vivo engineering of living tissues with adult stem cells. Tissue Eng. 12:3007–3019. 2006. View Article : Google Scholar
40	Caplan AI: Adult mesenchymal stem cells for tissue engineering versus regenerative medicine. J Cell Physiol. 213:341–347. 2007. View Article : Google Scholar : PubMed/NCBI
41	Eberli D and Atala A: Tissue engineering using adult stem cells. Methods Enzymol. 420:287–302. 2006. View Article : Google Scholar : PubMed/NCBI
42	Chang PC, Chien LY, Chong LY, Kuo YP and Hsiao JK: Glycated matrix up-regulates inflammatory signaling similarly to Porphyromonas gingivalis lipopolysaccharide. J Periodontal Res. 48:184–193. 2013. View Article : Google Scholar
43	Fan JZ, Wang Y, Meng Y, Li GW, Chang SX, Nian H and Liang YJ: Panax notoginseng saponins mitigate ovariectomy-induced bone loss and inhibit marrow adiposity in rats. Menopause. 22:1343–1350. 2015. View Article : Google Scholar : PubMed/NCBI
44	Lee JH, Baek HR, Lee KM, Zheng GB, Shin SJ and Shim HJ: Effects of ovariectomy and corticosteroid induced osteoporosis on the osteoinductivity of rhBMP-2 in a segmental long-bone defect model. Tissue Eng Part A. 21:2262–2271. 2015. View Article : Google Scholar : PubMed/NCBI
45	Fang J, Yang L, Zhang R, Zhu X and Wang P: Are there differences between Sprague-Dawley and Wistar rats in long-term effects of ovariectomy as a model for postmenopausal osteoporosis? Int J Clin Exp Pathol. 8:1491–1502. 2015.PubMed/NCBI
46	Liu Y, Wang L, Liu S, Liu D, Chen C, Xu X, Chen X and Shi S: Transplantation of SHED prevents bone loss in the early phase of ovariectomy-induced osteoporosis. J Dent Res. 93:1124–1132. 2014. View Article : Google Scholar : PubMed/NCBI
47	Bressan E, Ferroni L, Gardin C, Pinton P, Stellini E, Botticelli D, Sivolella S and Zavan B: Donor age-related biological properties of human dental pulp stem cells change in nanostructured scaffolds. PLoS One. 7:e491462012. View Article : Google Scholar : PubMed/NCBI
48	Sato C, Iso Y, Mizukami T, Otabe K, Sasai M, Kurata M, Sanbe T, Sekiya I, Miyazaki A and Suzuki H: Fibroblast growth factor-23 induces cellular senescence in human mesenchymal stem cells from skeletal muscle. Biochem Biophys Res Commun. 470:657–662. 2016. View Article : Google Scholar : PubMed/NCBI
49	Hong CJ, Park H and Yu SW: Autophagy for the quality control of adult hippocampal neural stem cells. Brain Res. March 9–2016.Epub ahead of print. View Article : Google Scholar
50	Takashima Y, Terada M, Udono M, Miura S, Yamamoto J and Suzuki A: Suppression of let-7b and miR-125a/b maturation by Lin28b enables maintenance of stem cell properties in hepatoblasts. Hepatology. March 17–2016.Epub ahead of print. View Article : Google Scholar : PubMed/NCBI
51	Larijani B, Arjmand B, Ahmadbeigi N, Falahzadeh K, Soleimani M, Sayahpour FA and Aghayan HR: A simple and cost-effective method for isolation and expansion of human fetal pancreas derived mesenchymal stem cells. Arch Iran Med. 18:770–775. 2015.PubMed/NCBI
52	Tong L, Zhou J, Rong L, Seeley EJ, Pan J, Zhu X, Liu J, Wang Q, Tang X, Qu J, et al: Fibroblast growth factor-10 (FGF-10) mobilizes lung-resident mesenchymal stem cells and protects against acute lung injury. Sci Rep. 6:216422016. View Article : Google Scholar : PubMed/NCBI
53	Drowley L, Koonce C, Peel S, Jonebring A, Plowright AT, Kattman SJ, Andersson H, Anson B, Swanson BJ, Wang QD and Brolen G: Human induced pluripotent stem cell-derived cardiac progenitor cells in phenotypic screening: A transforming growth factor-β type 1 receptor kinase inhibitor induces efficient cardiac differentiation. Stem Cells Transl Med. 5:164–174. 2016. View Article : Google Scholar
54	Tuganbekova S, Gaipov A, Turebekov Z, Saparbayev S, Shaimardanova G, Popova N, Taubaldiyeva Z, Serebrennikova D and Trimova R: Fetal renal stem cell transplant in nephrotic and nonnephrotic glomerulonephritis with stage 2–4 chronic kidney disease: Potential effect on proteinuria and glomerular filtration. rate. 13(Suppl 3): 156–159. 2015.