FTY720 enhances osteogenic differentiation of bone marrow mesenchymal stem cells in ovariectomized rats

Huang,Chuang; Ling,Rui; Li,Fei‑Jiang; Li,Er‑Cui; Huang,Qi‑Ke; Liu,Bao‑Gang; Ding,Yin; You,Si‑Wei

doi:10.3892/mmr.2016.5342

FTY720 enhances osteogenic differentiation of bone marrow mesenchymal stem cells in ovariectomized rats

Authors:
- Chuang Huang
- Rui Ling
- Fei‑Jiang Li
- Er‑Cui Li
- Qi‑Ke Huang
- Bao‑Gang Liu
- Yin Ding
- Si‑Wei You
View Affiliations

Affiliations: Department of Orthodontics, State Key Laboratory of Military Stomatology, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China, Department of General Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China, Department of Biomedical Engineering, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China, Department of Gastroenterology and Endocrinology, Shaanxi Provincial Armed Police Corps Hospital, Xi'an, Shaanxi 710032, P.R. China, Out‑Patient Department, General Hospital of The Second Artillery, Beijing 100820, P.R. China, Department of Ophthalmology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China
Published online on: May 24, 2016 https://doi.org/10.3892/mmr.2016.5342
Pages: 927-935

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

Sphingosine-1-phosphate and its structural analog FTY720 (fingolimod) are important in the inhibition of osteoclast differentiation and bone resorption, however, it remains unknown whether they enhance osteogenic differentiation of the bone marrow mesenchymal stem cells (BM‑MSCs). The present study investigated the effect of FTY720 on the osteogenic differentiation of BM‑MSCs from the femurs of the ovariectomized (OVX) rats. Three different concentrations (1, 10 and 100 nM) of FTY720 were demonstrated to markedly upregulate mRNA expression levels of Runt‑related transcription factor 2 (Runx2) and Sp7 transcription factor (Sp7) at 2 weeks, and alkaline phosphatase (ALP) at 3 weeks. The osteocalcin (OCN) expression was similar at weeks 2 and 3. The protein expression levels of Runx2, Sp7, OCN and ALP induced by three different concentrations of FTY720 were higher than those in the control groups at 3 weeks in the OVX and sham groups. The findings of the current study suggested a beneficial effect of FTY720 on bone formation in OVX rats, and provided a potential therapeutic method of FTY720 to prevent alveolar bone resorption in patients with post‑menopausal osteoporosis.

View Figures

View References

1	Rachner TD, Khosla S and Hofbauer LC: Osteoporosis: Now and the future. Lancet. 377:1276–1287. 2011. View Article : Google Scholar : PubMed/NCBI
2	Liang W, Li X, Li Y, Li C, Gao B, Gan H, Li S, Shen J, Kang J, Ding S, et al: Tongue coating microbiome regulates the changes in tongue texture and coating in patients with post-menopausal osteoporosis of Ganshen deficiency syndrome type. Int J Mol Med. 32:1069–1076. 2013.PubMed/NCBI
3	Khan AA, Morrison A, Hanley DA, Felsenberg D, McCauley LK, O'Ryan F, Reid IR, Ruggiero SL, Taguchi A, Tetradis S, et al: Diagnosis and management of osteonecrosis of the Jaw: A systematic review and international consensus. J Bone Miner Res. 30:3–23. 2015. View Article : Google Scholar
4	Sato C, Iwasaki T, Kitano S, Tsunemi S and Sano H: Sphingosine 1-phosphate receptor activation enhances BMP-2-induced osteoblast differentiation. Biochem Biophys Res Commun. 423:200–205. 2012. View Article : Google Scholar : PubMed/NCBI
5	Ishii M, Egen JG, Klauschen F, Meier-Schellersheim M, Saeki Y, Vacher J, Proia RL and Germain RN: Sphingosine-1-phosphate mobilizes osteoclast precursors and regulates bone homeostasis. Nature. 458:524–528. 2009. View Article : Google Scholar : PubMed/NCBI
6	Lotinun S, Kiviranta R, Matsubara T, Alzate JA, Neff L, Lüth A, Koskivirta I, Kleuser B, Vacher J, Vuorio E, et al: Osteoclast-specific cathepsin K deletion stimulates S1P-dependent bone formation. J Clin Invest. 123:666–681. 2013.PubMed/NCBI
7	Ryu J, Kim HJ, Chang EJ, Huang H, Banno Y and Kim HH: Sphingosine 1-phosphate as a regulator of osteoclast differentiation and osteoclast-osteoblast coupling. EMBO J. 25:5840–5851. 2006. View Article : Google Scholar : PubMed/NCBI
8	Mandala S, Hajdu R, Bergstrom J, Quackenbush E, Xie J, Milligan J, Thornton R, Shei GJ, Card D, Keohane C, et al: Alteration of lymphocyte trafficking by sphingosine-1-phosphate receptor agonists. Science. 296:346–349. 2002. View Article : Google Scholar : PubMed/NCBI
9	Venkataraman K, Lee YM, Michaud J, Thangada S, Ai Y, Bonkovsky HL, Parikh NS, Habrukowich C and Hla T: Vascular endothelium as a contributor of plasma sphingosine 1-phosphate. Circ Res. 102:669–676. 2008. View Article : Google Scholar : PubMed/NCBI
10	Poynton AR and Lane JM: Safety profile for the clinical use of bone morphogenetic proteins in the spine. Spine (Phila Pa 1976). 27(16 Suppl 1): S40–S48. 2002. View Article : Google Scholar
11	Meno-Tetang GM, Li H, Mis S, Pyszczynski N, Heining P, Lowe P and Jusko WJ: Physiologically based pharmacokinetic modeling of FTY720 (2-amino-2 [2-(-4-octylphenyl)ethyl] propane-1,3-diol hydrochloride) in rats after oral and intravenous doses. Drug Metab Dispos. 34:1480–1487. 2006. View Article : Google Scholar : PubMed/NCBI
12	Sefcik LS, Aronin CE, Awojoodu AO, Shin SJ, Mac Gabhann F, MacDonald TL, Wamhoff BR, Lynch KR, Peirce SM and Botchwey EA: Selective activation of sphingosine 1-phosphate receptors 1 and 3 promotes local microvascular network growth. Tissue Eng Part A. 17:617–629. 2011. View Article : Google Scholar :
13	Petrie Aronin CE, Shin SJ, Naden KB, Rios PD Jr, Sefcik LS, Zawodny SR, Bagayoko ND, Cui Q, Khan Y and Botchwey EA: The enhancement of bone allograft incorporation by the local delivery of the sphingosine 1-phosphate receptor targeted drug FTY720. Biomaterials. 31:6417–6424. 2010. View Article : Google Scholar : PubMed/NCBI
14	Petrie Aronin CE, Sefcik LS, Tholpady SS, Tholpady A, Sadik KW, Macdonald TL, Peirce SM, Wamhoff BR, Lynch KR, Ogle RC and Botchwey EA: FTY720 promotes local microvascular network formation and regeneration of cranial bone defects. Tissue Eng Part A. 16:1801–1809. 2010. View Article : Google Scholar
15	Turner AS: Animal models of osteoporosis-necessity and limitations. Eur Cell Mater. 1:66–81. 2001.
16	Thompson DD, Simmons HA, Pirie CM and Ke HZ: FDA Guidelines and animal models for osteoporosis. Bone. 17(Suppl 4): S125–S133. 1995. View Article : Google Scholar
17	National Research Council of the National Academies: Guide for the Care and Use of Laboratory Animals. 8th edition. The National Academies Press; Washington D.C.: 2011
18	Sims NA, Morris HA, Moore RJ and Durbridge TC: Increased bone resorption precedes increased bone formation in the ovariectomized rat. Calcif Tissue Int. 59:121–127. 1996. View Article : Google Scholar : PubMed/NCBI
19	Chen HL, Tung YT, Chuang CH, Tu MY, Tsai TC, Chang SY and Chen CM: Kefir improves bone mass and microarchitecture in an ovariectomized rat model of postmenopausal osteoporosis. Osteoporosis Int. 26:589–599. 2015. View Article : Google Scholar
20	Liu Y, Ming L, Luo H, Liu W, Zhang Y, Liu H and Jin Y: Integration of a calcined bovine bone and BMSC-sheet 3D scaffold and the promotion of bone regeneration in large defects. Biomaterials. 34:9998–10006. 2013. View Article : Google Scholar : 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	Miyazaki M, Hardjo M, Masaka T, Tomiyama K, Mahmut N, Medina RJ, Niida A, Sonegawa H, Du G, Yong R, et al: Isolation of a bone marrow-derived stem cell line with high proliferation potential and its application for preventing acute fatal liver failure. Stem Cells. 25:2855–2863. 2007. View Article : Google Scholar : PubMed/NCBI
23	Wu Y, Zhao RC and Tredget EE: Concise review: Bone marrow-derived stem/progenitor cells in cutaneous repair and regeneration. Stem Cells. 28:905–915. 2010.PubMed/NCBI
24	Wu C, Miron R, Sculean A, Kaskel S, Doert T, Schulze R and Zhang Y: Proliferation, differentiation and gene expression of osteoblasts in boron-containing associated with dexamethasone deliver from mesoporous bioactive glass scaffolds. Biomaterials. 32:7068–7078. 2011. View Article : Google Scholar : PubMed/NCBI
25	Zhao Z, Chen Z, Zhao X, Pan F, Cai M, Wang T, Zhang H, Lu JR and Lei M: Sphingosine-1-phosphate promotes the differentiation of human umbilical cord mesenchymal stem cells into cardiomyocytes under the designated culturing conditions. J Biomed Sci. 18:372011. View Article : Google Scholar : PubMed/NCBI
26	Nincheri P, Luciani P, Squecco R, Donati C, Bernacchioni C, Borgognoni L, Luciani G, Benvenuti S, Francini F and Bruni P: Sphingosine 1-phosphate induces differentiation of adipose tissue-derived mesenchymal stem cells towards smooth muscle cells. Cell Mol Life Sci. 66:1741–1754. 2009. View Article : Google Scholar : PubMed/NCBI
27	Sharma A, Meyer F, Hyvonen M, Best SM, Cameron RE and Rushton N: Osteoinduction by combining bone morphogenetic protein (BMP)-2 with a bioactive novel nanocomposite. Bone Joint Res. 1:145–151. 2012. View Article : Google Scholar
28	Sinha KM and Zhou X: Genetic and molecular control of osterix in skeletal formation. J Cell Biochem. 114:975–984. 2013. View Article : Google Scholar :
29	Jang H, Kim EJ, Park JK, Kim DE, Kim HJ, Sun WS, Hwang S, Oh KB, Koh JT, Jang WG and Lee JW: SMILE inhibits BMP-2-induced expression of osteocalcin by suppressing the activity of the RUNX2 transcription factor in MC3T3E1 cells. Bone. 61:10–18. 2014. View Article : Google Scholar : PubMed/NCBI
30	Matsuzaki E, Hiratsuka S, Hamachi T, Takahashi-Yanaga F, Hashimoto Y, Higashi K, Kobayashi M, Hirofuji T, Hirata M and Maeda K: Sphingosine-1-phosphate promotes the nuclear translocation of β-catenin and thereby induces osteoprotegerin gene expression in osteoblast-like cell lines. Bone. 55:315–324. 2013. View Article : Google Scholar : PubMed/NCBI
31	Hashimoto Y, Matsuzaki E, Higashi K, Takahashi-Yanaga F, Takano A, Hirata M and Nishimura F: Sphingosine-1-phosphate inhibits differentiation of C3H10T1/2 cells into adipocyte. Mol Cell Biochem. 401:39–47. 2015. View Article : Google Scholar
32	Komori T: Regulation of osteoblast differentiation by transcription factors. J Cell Biochem. 99:1233–1239. 2006. View Article : Google Scholar : PubMed/NCBI
33	Kido HW, Bossini PS, Tim CR, Parizotto NA, da Cunha AF, Malavazi I and Renno AC: Evaluation of the bone healing process in an experimental tibial bone defect model in ovariectomized rats. Aging Clin Exp Res. 26:473–481. 2014. View Article : Google Scholar : PubMed/NCBI