Advertisement

Molecular and Cellular Biochemistry

, Volume 462, Issue 1–2, pp 107–114 | Cite as

Vaspin protects mouse mesenchymal stem cells from oxidative stress-induced apoptosis through the MAPK/p38 pathway

  • Xiao Zhu
  • Lingyan Zhang
  • Youming Chen
  • Bo Chen
  • Haifeng Huang
  • Jicheng Lv
  • Shidi Hu
  • Jie ShenEmail author
Article
  • 95 Downloads

Abstract

The aim of the work was to study the influence of vaspin on oxidative stress-induced apoptosis of mouse mesenchymal stem cells (MSCs). MSCs originated from bone marrow of C57BL/6 mouse were treated with vaspin and/or H2O2 in a dose-dependent manner. Cellular viability detected by CCK-8 and cell apoptosis studied by flow cytometry and TUNEL assay were observed in these cells. The protein expressions of PI3K, p-PI3K, Akt, p-Akt, T-ERK1/2, p-ERK1/2, p38, p-p38, JNK, and p-JNK were tested by Western blot. Vaspin had no significant effect on cellular viability, but significantly reduced H2O2-induced apoptosis. Western blot assay showed that pretreatment with vaspin promoted the activation of p-p38. Inhibition of p38 by SB203580 suppressed the protective effect of vaspin on oxidative stress-induced apoptosis. Vaspin inhibits oxidative stress-induced apoptosis of MSCs via the activation of MAPK/p38 signaling pathway. These findings indicate that vaspin is prone to osteoporosis protection.

Keywords

Vaspin Mesenchymal stem cells Apoptosis 

Notes

Funding

This study was funded by the National Natural Science Foundation of China (Grant No. 81400849); the Natural Science Foundation of Guangdong Province (Grant No. 2014A030310490); the Science and Technology Planning Project of Guangdong Province, China (Grant No. 2017A020215189); the Science and Technology Planning Project of Tianhe District, Guangdong Province, China (Grant No. 2013kw004).

Compliance with ethical standards

Conflict of interest

The authors declare that they there are no competing interests.

References

  1. 1.
    Khosla S, Hofbauer LC (2017) Osteoporosis treatment: recent developments and ongoing challenges. Lancet Diabetes Endocrinol 5(11):898–907.  https://doi.org/10.1016/S2213-8587(17)30188-2 CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Phetfong J, Sanoranart T, Nartparayut K, Nimsanor N, Seenprachawong K, Prachayastittikul V, Supokawej A (2016) Osteoporosis: the current status of mesenchymal stem cell-based therapy. Cell Mol Biol Lett 21:12.  https://doi.org/10.1186/s11658-016-0013-1 CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Asatrian G, Pham D, Hardy WR, James AW, Peault B (2015) Stem cell technology for bone regeneration: current status and potential applications. Stem Cells Cloning 8:39–48.  https://doi.org/10.2147/SCCAA.S48423 CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Turgeman G, Zilberman Y, Zhou S, Kelly P, Moutsatsos IK, Kharode YP, Borella LE, Bex FJ, Komm BS, Bodine PV, Gazit D (2002) Systemically administered rhBMP-2 promotes MSC activity and reverses bone and cartilage loss in osteopenic mice. J Cell Biochem 86:461–474.  https://doi.org/10.1002/jcb.10231 CrossRefPubMedGoogle Scholar
  5. 5.
    Janderova L, McNeil M, Murrell AN, Mynatt RL, Smith SR (2003) Human mesenchymal stem cells as an in vitro model for human adipogenesis. Obes Res 11:65–74.  https://doi.org/10.1038/oby.2003.11 CrossRefPubMedGoogle Scholar
  6. 6.
    Hung SC, Chang CF, Ma HL, Chen TH, Low-Tone Ho L (2004) Gene expression profiles of early adipogenesis in human mesenchymal stem cells. Gene 340:141–150.  https://doi.org/10.1016/j.gene.2004.06.028 CrossRefPubMedGoogle Scholar
  7. 7.
    Huang Q, Gao B, Jie Q, Wei BY, Fan J, Zhang HY, Zhang JK, Li XJ, Shi J, Luo ZJ, Yang L, Liu J (2014) Ginsenoside-Rb2 displays anti-osteoporosis effects through reducing oxidative damage and bone-resorbing cytokines during osteogenesis. Bone 66:306–314.  https://doi.org/10.1016/j.bone.2014.06.010 CrossRefPubMedGoogle Scholar
  8. 8.
    Guan H, Zhao L, Cao H, Chen A, Xiao J (2015) Epoxyeicosanoids suppress osteoclastogenesis and prevent ovariectomy-induced bone loss. FASEB J 29:1092–1101.  https://doi.org/10.1096/fj.14-262055 CrossRefPubMedGoogle Scholar
  9. 9.
    Joo JH, Huh JE, Lee JH, Lee SG, Choi S, Lee HJ, Song SW, Jeong Y, Goo JI, Choi Y, Baek HK, Yi SS, Park SJ, Lee JE, Ku SK, Lee WJ, Lee KI, Lee SY, Bae YS (2016) A novel pyrazole derivative protects from ovariectomy-induced osteoporosis through the inhibition of NADPH oxidase. Sci Rep 6:22389.  https://doi.org/10.1038/srep22389 CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Stenderup K, Justesen J, Clausen C, Kassem M (2003) Aging is associated with decreased maximal life span and accelerataed senescence of bone marrow stromal cells. Bone 33:919–926CrossRefGoogle Scholar
  11. 11.
    Zhang JK, Yang L, Meng GL, Yuan Z, Fan J, Li D, Chen JZ, Shi TY, Hu HM, Wei BY et al (2013) Protection by salidroside against bone loss via inhibition of oxidative stress and bone-resorbing mediators. PLoS ONE 8:e57251.  https://doi.org/10.1371/journal.pone.0057251 CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Schröder K (2015) NADPH oxidases in bone homeostasis and osteoporosis. Cell Mol Life Sci 72:25–38.  https://doi.org/10.1007/s00018-014-1712-2 CrossRefPubMedGoogle Scholar
  13. 13.
    Hida K, Wada J, Eguchi J, Zhang H, Baba M, Seida A, Hashimoto I, Okada T, Yasuhara A, Nakatsuka A, Shikata K, Hourai S, Futami J, Watanabe E, Matsuki Y, Hiramatsu R, Akagi S, Makino H, Kanwar YS (2005) Visceral adipose tissue-derived serine protease inhibitor: a unique insulin-sensitizing adipocytokine in obesity. Proc Natl Acad Sci USA 102:10610–10615.  https://doi.org/10.1073/pnas.0504703102 CrossRefPubMedGoogle Scholar
  14. 14.
    Jung CH, Lee WJ, Hwang JY, Seol SM, Kim YM, Lee YL, Park JY (2011) Vaspin protects vascular endothelial cells against free fatty acid-induced apoptosis through a phosphatidylinositol 3-kinase/Akt pathway. Biochem Biophys Res Commun 413:264–269.  https://doi.org/10.1016/j.bbrc.2011.08.083 CrossRefPubMedGoogle Scholar
  15. 15.
    Lin Y, Zhuang J, Li H, Zhu G, Zhou S, Li W, Peng W, Xu Y (2016) Vaspin attenuates the progression of atherosclerosis by inhibiting ER stress-induced macrophage apoptosis in apoE-/- mice. Mol Med Rep 13:1509–1516.  https://doi.org/10.3892/mmr.2015.4708 CrossRefPubMedGoogle Scholar
  16. 16.
    Li H, Peng WH, Zhuang JH, Lu Y, Jian W, Wei Y, Li W, Xu Y (2013) Vaspin attenuates high glucose-induced vascular smooth muscle cells proliferation and chemokinesis by inhibiting the MAPK, PI3 K/Akt, and NF-κB signaling pathways. Atherosclerosis 228:61–68.  https://doi.org/10.1016/j.atherosclerosis.2013.02.013 CrossRefPubMedGoogle Scholar
  17. 17.
    Liu S, Dong Y, Wang T, Zhao S, Yang K, Chen X, Zheng C (2014) Vaspin inhibited proinflammatory cytokine induced activation of nuclear factor-kappa B and its downstream molecules in human endothelial EA.hy926 cell. Diabetes Res Clin Pract 103:482–488.  https://doi.org/10.1016/j.diabres.2013.12.002 CrossRefPubMedGoogle Scholar
  18. 18.
    Sun N, Wang H, Wang L (2015) Vaspin alleviates dysfunction of endothelial progenitor cells induced by high glucose via PI3 K/Akt/eNOS pathway. Int J Clin Exp Pathol 8:482–489PubMedPubMedCentralGoogle Scholar
  19. 19.
    Jung CH, Lee MJ, Kang YM, Lee YL, Yoon HK, Kang SW, Lee WJ, Park JY (2014) Vaspin inhibits cytokine-induced nuclear factor-kappa B activation and adhesion molecule expression via AMP-activated protein kinase activation in vascular endothelial cell. Cardiovasc Diabetol 13:41.  https://doi.org/10.1186/1475-2840-13-41 CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Zhu X, Jiang Y, Shan PF, Shen J, Liang QH, Cui RR, Liu Y, Liu GY, Wu SS, Lu Q, Xie H, Liu YS, Yuan LQ, Liao EY (2013) Vaspin attenuates the apoptosis of human osteoblasts through ERK signaling pathway. Amino Acids 44:961–968.  https://doi.org/10.1007/s00726-012-1425-5 CrossRefPubMedGoogle Scholar
  21. 21.
    Liu Y, Xu F, Pei HX, Zhu X, Lin X, Song CY, Liang QH, Liao EY, Yuan LQ (2016) Vaspin regulates the osteogenic differentiation of MC3T3-E1 through the PI3 K-Akt/miR-34c loop. Sci Rep 6:25578.  https://doi.org/10.1038/srep25578 CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Kamio N, Kawato T, Tanabe N, Kitami S, Morita T, Ochiai K, Maeno M (2013) Vaspin attenuates RANKL-induced osteoclast formation in RAW264.7 cells. Connect Tiss Res 54:147–152.  https://doi.org/10.3109/03008207.2012.761978 CrossRefGoogle Scholar
  23. 23.
    Sun S, Guo Z, Xiao X, Liu B, Liu X, Tang PH, Mao N (2003) Isolation of mouse marrow mesenchymal progenitors by a novel and reliable method. Stem Cells 21:527–535.  https://doi.org/10.1634/stemcells.21-5-527 CrossRefPubMedGoogle Scholar
  24. 24.
    Turgeman G, Zilberman Y, Zhou S, Kelly P, Moutsatsos IK, Kharode YP, Borella LE, Bex FJ, Komm BS, Bodine PV, Gazit D (2002) Systemically administered rhBMP-2 promotes MSC activity and reverses bone and cartilage loss in osteopenic mice. J Cell Biochem 86:461–474.  https://doi.org/10.1002/jcb.10231 CrossRefPubMedGoogle Scholar
  25. 25.
    Baek KH, Oh KW, Lee WY, Lee SS, Kim MK, Kwon HS, Rhee EJ, Han JH, Song KH, Cha BY, Lee KW, Kang MI (2010) Association of oxidative stress with postmenopausal osteoporosis and the effects of hydrogen peroxide on osteoclast formation in human bone marrow cell cultures. Calcif Tissue Int 87:226–235.  https://doi.org/10.1007/s00223-010-9393-9 CrossRefPubMedGoogle Scholar
  26. 26.
    Stolzing A, Jones E, McGonagle D, Scutt A (2008) Age-related changes in human bone marrow-derived mesenchymal stem cells: consequences for cell therapies. Mech Ageing Dev 129:163–173.  https://doi.org/10.1016/j.mad.2007.12.002 CrossRefPubMedGoogle Scholar
  27. 27.
    Jin YQ, Li JL, Chen JD, Xu CL, Li H (2017) Dalbergiodin (DAL) protects MC3T3-E1 osteoblastic cells against H2O2-induced cell damage through activation of the PI3 K/Akt/SMAD1 pathway. Naunyn Schmiedebergs Arch Pharmacol 390:711–720.  https://doi.org/10.1007/s00210-017-1365-4 CrossRefPubMedGoogle Scholar
  28. 28.
    Arai M, Shibata Y, Pugdee K, Abiko Y, Ogata Y (2007) Effects of reactive oxygen species (ROS) on antioxidant system and osteoblastic differentiation in MC3T3-E1 cells. IUBMB Life 59:27–33.  https://doi.org/10.1080/15216540601156188 CrossRefPubMedGoogle Scholar
  29. 29.
    Zhong ZM, Bai L, Chen JT (2009) Advanced oxidation protein products inhibit proliferation and differentiation of rat osteoblast-like cells via NF-kappaB pathway. Cell Physiol Biochem 24:105–114.  https://doi.org/10.1159/000227818 CrossRefPubMedGoogle Scholar
  30. 30.
    Mody N, Parhami F, Sarafian TA, Demer LL (2001) Oxidative stress modulates osteoblastic differentiation of vascular and bone cells. Free Radic Biol Med 31:509–519CrossRefGoogle Scholar
  31. 31.
    Weinstein RS, Jilka RL, Parfitt AM, Manolagas SC (1998) Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts end osteocytes by glucocorticoids. Potential mechanisms of their deleterious effects on bone. J Clin Invest 102:274–282.  https://doi.org/10.1172/JCI2799 CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Lee NK, Choi YG, Baik JY, Han SY, Jeong DW, Bae YS, Kim N, Lee SY (2005) A crucial role for reactive oxygen species in RANKL-induced osteoclast differentiation. Blood 106:852–859.  https://doi.org/10.1182/blood-2004-09-3662 CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Alp HH, Huyut Z, Yildirim S, Basbugan Y, Ediz L, Sekeroģlu MR (2017) The effect of PDE5 inhibitors on bone and oxidative damage in ovariectomy-induced osteoporosis. Exp Biol Med (Maywood) 242:1051–1061.  https://doi.org/10.1177/1535370217703352 CrossRefGoogle Scholar
  34. 34.
    Lv M, Liu Y, Xiao TH, Jiang W, Lin BW, Zhang XM, Lin YM, Xu ZS (2017) GYY4137 stimulates osteoblastic cell proliferation and differentiation via an ERK1/2-dependent anti-oxidant mechanism. Am J Trans Res 15:1183–1192Google Scholar
  35. 35.
    Jezek P, Hlavata L (2005) Mitochondria in homeostasis of reactive oxygen species in cell, tissues, and organism. Int J Biochem Cell Biol 37:2478–2503.  https://doi.org/10.1016/j.biocel.2005.05.013 CrossRefPubMedGoogle Scholar
  36. 36.
    Sui XB, Kong N, Ye L et al (2014) P38 and JNK MAPK pathways control the balance of apoptosis and autophagy in response to chemotherapeutic agents. Cancer Lett 344(2):174–179CrossRefGoogle Scholar
  37. 37.
    Limami Y, Pinon A, Leger DY et al (2012) The P2Y2/Src/p38/COX-2 pathway is involved in the resistance to ursolic acid-induced apoptosis in colorectal and prostate cancer cells. Biochimie 94(8):1754–1763CrossRefGoogle Scholar
  38. 38.
    Gan L, Wang J, Xu H et al (2011) Resistance to docetaxel-induced apoptosis in prostate cancer cells by p38/p53/p21 signaling. Prostate 71(11):1158–1166CrossRefGoogle Scholar
  39. 39.
    Chen SF, Nieh S, Jao SW et al (2012) Quercetin suppresses drug-resistant spheres via the p38 MAPK-Hsp27 apoptotic pathway in oral cancer cells. PLoS ONE 7(11):e49275CrossRefGoogle Scholar
  40. 40.
    Salim H, Akbar NS, Zong D et al (2012) MiRNA-214 modulates radiotherapy response of non-small cell lung cancer cells through regulation of p38 MAPK, apoptosis and senescence. Br J Cancer 107(8):1361–1373CrossRefGoogle Scholar
  41. 41.
    Song Z, Ma J, Lu Y et al (2019) The protective role of the MKP-5-JNK/P38 pathway in glucolipotoxicity-induced islet β-cell dysfunction and apoptosis. Exp Cell Res.  https://doi.org/10.1016/j.yexcr.2019.06.012 CrossRefPubMedGoogle Scholar
  42. 42.
    Xiao X, Cheng Y, Song D et al (2019) Selenium-enriched Bacillus paralicheniformis SR14 attenuates H2O2-induced oxidative damage in porcine jejunum epithelial cells via the MAPK pathway. Appl Microbiol Biotechnol.  https://doi.org/10.1007/s00253-019-09922-9 CrossRefPubMedGoogle Scholar
  43. 43.
    Liu J, Chang F, Li F et al (2015) Palmitate promotes autophagy and apoptosis through ROS-dependent JNK and p38 MAPK. BBRC 463(3):262–267PubMedGoogle Scholar
  44. 44.
    Zhu GL, Liu YM, Zhi Y et al (2019) PKA- and Ca2 + -dependent p38 MAPK/CREB activation protects against manganese-mediated neuronal apoptosis. Toxicol Lett 309:10–19CrossRefGoogle Scholar
  45. 45.
    Zhang LL, Meng QH, Yepuri N et al (2018) Surfactant proteins-A and -D attenuate LPS-induced apoptosis in primary intestinal epithelial cells (IECs). Shock 49(1):90–98CrossRefGoogle Scholar
  46. 46.
    Shi JR, Guan J, Jiang BB et al (2010) Amyloidogenic light chains induce cardiomyocyte contractile dysfunction and apoptosis via a non-canonical p38α MAPK pathway. Proc Natl Acad Sci USA 107(9):4188–4193CrossRefGoogle Scholar
  47. 47.
    Cong Q, Jia H, Biswas S, Li P, Qiu S, Deng Q, Guo X, Ma G, Ling Chau JF, Wang Y, Zhang ZL, Jiang X, Liu H, Li B (2016) p38α MAPK regulates lineage commitment and OPG synthesis of bone marrow stromal cells to prevent bone loss under physiological and pathological conditions. Stem Cell Rep 6:566–578.  https://doi.org/10.1016/j.stemcr.2016.02.001 CrossRefGoogle Scholar
  48. 48.
    Kim JY, Lee JS, Han YS, Lee JH, Bael I, Yoon YM, Kwon SM, Lee SH (2015) Pretreatment with Lycopene attenuates oxidative stress-induced apoptosis in human mesenchymal stem cells. Biomol Ther (Seoul) 23:517–524.  https://doi.org/10.4062/biomolther.2015.085 CrossRefGoogle Scholar
  49. 49.
    Jiang H, Liang C, Liu X, Jiang Q, He Z, Wu J, Pan X, Ren Y, Fan M, Li M, Wu Z (2010) Palmitic acid promotes endothelial progenitor cells apoptosis via p38 and JNK mitogen-activated protein kinase pathways. Atherosclerosis 210:71–77.  https://doi.org/10.1016/j.atherosclerosis.2009.10.032 CrossRefPubMedGoogle Scholar
  50. 50.
    De Chiara G, Marcocci ME, Torcia M, Lucibello M, Rosini P, Bonini P, Higashimoto Y, Damonte G, Armirotti A, Amodei S, Palamara AT, Russo T, Garaci E, Cozzolino F (2006) Bcl-2 phosphorylation by p38 mapk: identification of target sites and biologic consequences. J Biol Chem 281:21353–21361CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Endocrinology and MetabolismThe Third Affiliated Hospital of Southern Medical UniversityGuangzhouChina
  2. 2.Department of Medical ImageThe Third Affiliated Hospital of Southern Medical UniversityGuangzhouChina
  3. 3.Department of Medical LaboratoryThe Third Affiliated Hospital of Southern Medical UniversityGuangzhouChina
  4. 4.Department of EndocrinologyGuangdong Second Provincial HospitalGuangzhouChina
  5. 5.Department of Internal MedicineThe First Affiliated Hospital of Sun Yat-Sen UniversityGuangzhouChina

Personalised recommendations