Tenascin-C expression and its associated pathway in BMSCs following co-culture with mechanically stretched ligament fibroblasts

Zhao,Bing; Hu,Mengcai; Wu,Huiyan; Ren,Chenchen; Wang,Jianshe; Cui,Shihong

doi:10.3892/mmr.2017.6329

Tenascin-C expression and its associated pathway in BMSCs following co-culture with mechanically stretched ligament fibroblasts

Authors:
- Bing Zhao
- Mengcai Hu
- Huiyan Wu
- Chenchen Ren
- Jianshe Wang
- Shihong Cui
View Affiliations

Affiliations: Department of Obstetrics, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China, Department of Clinical Medicine, Hebi Polytechnic College, Hebi, Henan 458030, P.R. China
Published online on: March 15, 2017 https://doi.org/10.3892/mmr.2017.6329
Pages: 2465-2472
Copyright: © Zhao 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

The occurrence of pelvic organ prolapse (POP) is closely associated with alterations in the extracellular matrix proteins of the supporting ligament. Bone marrow mesenchymal stem cells (BMSCs) have the potential to differentiate into a variety of cell types, including osteoblasts, chondroblasts and adipocytes. Therefore, BMSCs have the potential to improve the clinical outcomes of POP. Tenascin‑C is a large glycoprotein that is present in the ECM and is involved in morphogenetic movements, and tissue patterning and repair. The aim of the present study was to investigate the effect of mechanical stretching on tenascin‑C expression during the differentiation of BMSCs induced by pelvic ligament fibroblasts. BMSCs were isolated from 7‑day‑old Sprague Dawley rats. Fibroblasts were obtained from rat pelvic ligaments and, at the fourth passage, were subjected to 10% deformation with 1 Hz, periodic one‑way mechanical stretch stimulation, followed by co‑culture with BMSCs. The co‑culture with stretched fibroblasts increased tenascin‑C and transforming growth factor (TGF)‑β expression levels, compared with groups without mechanical stimulation. Neutralizing anti‑TGF‑β1 antibodies, and inhibitors of TGF‑β receptor, mitogen‑activated protein kinase (MAPK) kinase and MAPK, decreased tenascin‑C expression levels induced by TGF‑β and mechanical stretching. The results of the present study suggested that the regulation of tenascin‑C expression levels in BMSCs co‑cultured with mechanically stretched pelvic ligament fibroblasts is mediated via the soluble growth factor TGF‑β and the MAPK signaling pathway. In addition, these results indicated that in an indirect co‑culture system, pelvic ligament fibroblasts with mechanical stretch stimulation may promote the synthesis of tenascin‑C and BMSC differentiation into pelvic ligament fibroblasts.

View Figures

View References

1	Choi KH and Hong JY: Management of pelvic organ prolapse. Korean J Urol. 55:693–702. 2014. View Article : Google Scholar : PubMed/NCBI
2	Giarenis I and Robinson D: Prevention and management of pelvic organ prolapse. F1000Prime Rep. 6:772014. View Article : Google Scholar : PubMed/NCBI
3	Wiegersma M, Panman CM, Kollen BJ, Berger MY, Lisman-Van Leeuwen Y and Dekker JH: Effect of pelvic floor muscle training compared with watchful waiting in older women with symptomatic mild pelvic organ prolapse: Randomised controlled trial in primary care. BMJ. 349:g73782014. View Article : Google Scholar : PubMed/NCBI
4	Zhou Y, Ling O and Bo L: Expression and significance of lysyl oxidase-like 1 and fibulin-5 in the cardinal ligament tissue of patients with pelvic floor dysfunction. J Biomed Res. 27:23–28. 2013. View Article : Google Scholar : PubMed/NCBI
5	Aznal SS, Meng FG, Nalliah S, Tay A, Chinniah K and Jamli MF: Biochemical evaluation of the supporting structure of pelvic organs in selected numbers of premenopausal and postmenopausal Malaysian women. Indian J Pathol Microbiol. 55:450–455. 2012. View Article : Google Scholar : PubMed/NCBI
6	Wynn RF, Hart CA, Corradi-Perini C, O'Neill L, Evans CA, Wraith JE, Fairbairn LJ and Bellantuono I: A small proportion of mesenchymal stem cells strongly expresses functionally active CXCR4 receptor capable of promoting migration to bone marrow. Blood. 104:2643–2645. 2004. View Article : Google Scholar : PubMed/NCBI
7	Xu YX, Chen L, Hou WK, Lin P, Sun L, Sun Y, Dong QY, Liu JB and Fu YL: Mesenchymal stem cells treated with rat pancreatic extract secrete cytokines that improve the glycometabolism of diabetic rats. Transplant Proc. 41:1878–1884. 2009. View Article : Google Scholar : PubMed/NCBI
8	Miller MD, Nichols T and Butler CA: Patella fracture and proximal patellar tendon rupture following arthroscopic anterior cruciate ligament reconstruction. Arthroscopy. 15:640–643. 1999. View Article : Google Scholar : PubMed/NCBI
9	Omoto M, Miyashita H, Shimmura S, Higa K, Kawakita T, Yoshida S, McGrogan M, Shimazaki J and Tsubota K: The use of human mesenchymal stem cell-derived feeder cells for the cultivation of transplantable epithelial sheets. Invest Ophthalmol Vis Sci. 50:2109–2115. 2009. View Article : Google Scholar : PubMed/NCBI
10	Young RG, Butler DL, Weber W, Caplan AI, Gordon SL and Fink DJ: Use of mesenchymal stem cells in a collagen matrix for Achilles tendon repair. J Orthop Res. 16:406–413. 1998. View Article : Google Scholar : PubMed/NCBI
11	Hankemeier S, Hurschler C, Zeichen J, van Griensven M, Miller B, Meller R, Ezechieli M, Krettek C and Jagodzinski M: Bone marrow stromal cells in a liquid fibrin matrix improve the healing process of patellar tendon window defects. Tissue Eng Part A. 15:1019–1030. 2009. View Article : Google Scholar : PubMed/NCBI
12	Kushida T and Iida H: Bone marrow cell transplantation efficiently repairs tendon and ligament injuries. Front Cell Dev Biol. 2:272014. View Article : Google Scholar : PubMed/NCBI
13	Humphrey JD, Dufresne ER and Schwartz MA: Mechanotransduction and extracellular matrix homeostasis. Nat Rev Mol Cell Biol. 15:802–812. 2014. View Article : Google Scholar : PubMed/NCBI
14	Provenzano PP and Keely PJ: Mechanical signaling through the cytoskeleton regulates cell proliferation by coordinated focal adhesion and Rho GTPase signaling. J Cell Sci. 124:1195–1205. 2011. View Article : Google Scholar : PubMed/NCBI
15	Hwang Y and Barakat AI: Dynamics of mechanical signal transmission through prestressed stress fibers. PLoS One. 7:e353432012. View Article : Google Scholar : PubMed/NCBI
16	Horiguchi M, Ota M and Rifkin DB: Matrix control of transforming growth factor-β function. J Biochem. 152:321–329. 2012. View Article : Google Scholar : PubMed/NCBI
17	Midwood KS and Orend G: The role of tenascin-C in tissue injury and tumorigenesis. J Cell Commun Signal. 3:287–310. 2009. View Article : Google Scholar : PubMed/NCBI
18	Mackie EJ, Halfter W and Liverani D: Induction of tenascin in healing wounds. J Cell Biol. 107:2757–2767. 1988. View Article : Google Scholar : PubMed/NCBI
19	Imanaka-Yoshida K and Aoki H: Tenascin-C and mechanotransduction in the development and diseases of cardiovascular system. Front Physiol. 5:2832014. View Article : Google Scholar : PubMed/NCBI
20	Wang SJ, Zhu B, Ren XX, Ben H, Li YQ and Li YH: Effect of acupuncture of different acupoints on electrical activities of hypothalamic sexual arousal stimulation-related neurons at different stages of oestrous cycle in rats. Zhen Ci Yan Jiu. 32:313–318. 2007.(In Chinese). PubMed/NCBI
21	Bing Z, Linlin L, Jianguo Y, Shenshen R, Ruifang R and Xi Z: Effect of mechanical stretch on the expressions of elastin, LOX and Fibulin-5 in rat BMSCs with ligament fibroblasts co-culture. Mol Biol Rep. 39:6077–6085. 2012. View Article : Google Scholar : PubMed/NCBI
22	Zaminy A, Kashani Ragerdi I, Barbarestani M, Hedayatpour A, Mahmoudi R and Nejad Farzaneh A: Osteogenic differentiation of rat mesenchymal stem cells from adipose tissue in comparison with bone marrow mesenchymal stem cells: Melatonin as a differentiation factor. Iran Biomed J. 12:133–141. 2008.PubMed/NCBI
23	Jeong JY, Suresh S, Park MN, Jang M, Park S, Gobianand K, You S, Yeon SH and Lee HJ: Effects of capsaicin on adipogenic differentiation in bovine bone marrow mesenchymal stem cell. Asian-Australas J Anim Sci. 27:1783–1793. 2014. View Article : Google Scholar : PubMed/NCBI
24	Wilson E, Mai Q, Sudhir K, Weiss RH and Ives HE: Mechanical strain induces growth of vascular smooth muscle cells via autocrine action of PDGF. J Cell Biol. 123:741–747. 1993. View Article : Google Scholar : PubMed/NCBI
25	Millward-Sadler SJ, Wright MO, Lee H, Nishida K, Caldwell H, Nuki G and Salter DM: Integrin-regulated secretion of interleukin 4: A novel pathway of mechanotransduction in human articular chondrocytes. J Cell Biol. 145:183–189. 1999. View Article : Google Scholar : PubMed/NCBI
26	Yamamoto K, Dang QN, Kennedy SP, Osathanondh R, Kelly RA and Lee RT: Induction of tenascin-C in cardiac myocytes by mechanical deformation. Role of reactive oxygen species. J Biol Chem. 274:21840–21846. 1999. View Article : Google Scholar : PubMed/NCBI
27	Heid CA, Stevens J, Livak KJ and Williams PM: Real time quantitative PCR. Genome Res. 6:986–994. 1996. View Article : Google Scholar : PubMed/NCBI
28	Gibson UE, Heid CA and Williams PM: A novel method for real time quantitative RT-PCR. Genome Res. 6:995–1001. 1996. View Article : Google Scholar : PubMed/NCBI
29	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 : PubMed/NCBI
30	Ren CC, Ren RF, Zhao B, Zhang X and Jiang YJ: Study on oriented differentiation of bone marrow mesenchymal stem cells by fibroblast in rat uterine ligament with mechanical stretch. Zhonghua Fu Chan Ke Za Zhi. 46:527–532. 2011.(In Chinese). PubMed/NCBI
31	Wang JH, Thampatty BP, Lin JS and Im HJ: Mechanoregulation of gene expression in fibroblasts. Gene. 391:1–15. 2007. View Article : Google Scholar : PubMed/NCBI
32	Chiquet M, Gelman L, Lutz R and Maier S: From mechanotransduction to extracellular matrix gene expression in fibroblasts. Biochim Biophys Acta. 1793:911–920. 2009. View Article : Google Scholar : PubMed/NCBI
33	Jinnin M, Ihn H, Asano Y, Yamane K, Trojanowska M and Tamaki K: Tenascin-C upregulation by transforming growth factor-beta in human dermal fibroblasts involves Smad3, Sp1, and Ets1. Oncogene. 23:1656–1667. 2004. View Article : Google Scholar : PubMed/NCBI
34	Ewies AA, Al-Azzawi F and Thompson J: Changes in extracellular matrix proteins in the cardinal ligaments of post-menopausal women with or without prolapse: A computerized immunohistomorphometric analysis. Hum Reprod. 18:2189–2195. 2003. View Article : Google Scholar : PubMed/NCBI
35	Boreham MK, Wai CY, Miller RT, Schaffer JI and Word RA: Morphometric properties of the posterior vaginal wall in women with pelvic organ prolapse. Am J Obstet Gynecol. 187:1501–1509. 2002. View Article : Google Scholar : PubMed/NCBI
36	Kon E, Filardo G, Roffi A, Andriolo L and Marcacci M: New trends for knee cartilage regeneration: From cell-free scaffolds to mesenchymal stem cells. Curr Rev Musculoskelet Med. 5:236–243. 2012. View Article : Google Scholar : PubMed/NCBI
37	Lee IC, Wang JH, Lee YT and Young TH: The differentiation of mesenchymal stem cells by mechanical stress or/and co-culture system. Biochem Biophys Res Commun. 352:147–152. 2007. View Article : Google Scholar : PubMed/NCBI
38	Goepel C: Differential elastin and tenascin immunolabeling in the uterosacral ligaments in postmenopausal women with and without pelvic organ prolapse. Acta Histochem. 110:204–209. 2008. View Article : Google Scholar : PubMed/NCBI
39	Chiquet M, Sarasa-Renedo A and Tunc-Civelek V: Induction of tenascin-C by cyclic tensile strain versus growth factors: Distinct contributions by Rho/ROCK and MAPK signaling pathways. Biochim Biophys Acta. 1693:193–204. 2004. View Article : Google Scholar : PubMed/NCBI
40	Chiquet-Ehrismann R and Chiquet M: Tenascins: Regulation and putative functions during pathological stress. J Pathol. 200:488–499. 2003. View Article : Google Scholar : PubMed/NCBI
41	Lindahl GE, Chambers RC, Papakrivopoulou J, Dawson SJ, Jacobsen MC, Bishop JE and Laurent GJ: Activation of fibroblast procollagen alpha 1(I) transcription by mechanical strain is transforming growth factor-beta-dependent and involves increased binding of CCAAT-binding factor (CBF/NF-Y) at the proximal promoter. J Biol Chem. 277:6153–6161. 2002. View Article : Google Scholar : PubMed/NCBI
42	Zhang YE: Non-Smad pathways in TGF-beta signaling. Cell Res. 19:128–139. 2009. View Article : Google Scholar : PubMed/NCBI
43	Li H, Yu B, Zhang Y, Pan Z, Xu W and Li H: Jagged1 protein enhances the differentiation of mesenchymal stem cells into cardiomyocytes. Biochem Biophys Res Commun. 341:320–325. 2006. View Article : Google Scholar : PubMed/NCBI