Mechano growth factor promotes the differentiation of bone marrow mesenchymal stem cells into osteoblasts

doi:10.3969/j.issn.2095-4344.2016.32.001

Abstract

Abstract:

BACKGROUND: Mechano growth factor has the potential to activate muscle satellite cells and promote myogenic cell growth, and has dual roles in maintaining bone mass and repairing bone defects.
OBJECTIVE: To explore the mechanism underlying osteogenic differentiation of rabbit bone marrow mesenchymal stem cells promoted by the mechano growth factor.
METHODS: The best concentration and time of mechano growth factor to promote osteogenic differentiation of rabbit bone marrow mesenchymal stem cells were detected by MTT. The mRNA and protein expressions of alkaline phosphatase and osteocalcin were detected by qPCR and western blot, respectively. The phosphorylation level of AKT and mTOR were detected by western blot assay.
RESULTS AND CONCLUSION: The best concentration and time of mechano growth factor was 45 μg/L and 5 days for promoting the osteogenic differentiation of rabbit bone marrow mesenchymal stem cells. The expressions of alkaline phosphatase and osteocalcin at mRNA and protein levels were highest after 4-hour intervention with 45 μg/L mechano growth factor, and meanwhile, the phosphorylation levels of mTOR and AKT were also highest. These findings indicate that the mechano growth factor can promote the differentiation of rabbit bone marrow mesenchymal stem cells into osteoblasts via PI3K/AKT pathway, and its best concentration and time are 45 μg/L and 4 hours, respectively.

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

Key words: Cell Differentiation, Alkaline Phosphatase, Tissue Engineering

CLC Number:

R394.2

Tong Yan-xiang, Feng Wei, Jia Yan-fei, Wang Cai-xia, Lv Hui-cheng, Wu Yi-min, Jiang Dian-ming. Mechano growth factor promotes the differentiation of bone marrow mesenchymal stem cells into osteoblasts[J]. Chinese Journal of Tissue Engineering Research, 2016, 20(32): 4717-4724.

Figures/Tables 2

References

[1] Armakolas A, Philippou A, Panteleakou Z, et al. Preferential expression of IGF-1Ec (MGF) transcript in cancerous tissues of human prostate: evidence for a novel and autonomous growth factor activity of MGF E peptide in human prostate cancer cells. Prostate. 2010; 70(11):1233-1242.
[2] Kandalla PK, Goldspink G, Butler-Browne G, et al. Mechano Growth Factor E peptide (MGF-E), derived from an isoform of IGF-1, activates human muscle progenitor cells and induces an increase in their fusion potential at different ages. Mech Ageing Dev. 2011; 132(4):154-162.
[3] Deng M, Zhang B, Wang K, et al. Mechano growth factor E peptide promotes osteoblasts proliferation and bone-defect healing in rabbits. Int Orthop. 2011;35(7): 1099-1106.
[4] Peng Q, Qiu J, Sun J, et al. The nuclear localization of MGF receptor in osteoblasts under mechanical stimulation. Mol Cell Biochem. 2012;369(1-2): 147-156.
[5] Li C, Vu K, Hazelgrove K, et al. Increased IGF-IEc expression and mechano-growth factor production in intestinal muscle of fibrostenotic Crohn's disease and smooth muscle hypertrophy. Am J Physiol Gastrointest Liver Physiol. 2015;309(11):G888-899.
[6] Li H, Lei M, Luo Z, et al. Mechano-growth factor enhances differentiation of bone marrow-derived mesenchymal stem cells. Biotechnol Lett. 2015;37(11): 2341-2348.
[7] Luo Z, Jiang L, Xu Y, et al. Mechano growth factor (MGF) and transforming growth factor (TGF)-β3 functionalized silk scaffolds enhance articular hyaline cartilage regeneration in rabbit model. Biomaterials. 2015;52:463-475.
[8] Goldspink G. Research on mechano growth factor: its potential for optimising physical training as well as misuse in doping. Br J Sports Med. 2005;39(11): 787-788; discussion 787-788.
[9] Gan ZY, Fitter S, Vandyke K, et al. The effect of the dual PI3K and mTOR inhibitor BEZ235 on tumour growth and osteolytic bone disease in multiple myeloma. Eur J Haematol. 2015;94(4):343-354.
[10] Heras-Sandoval D, Pérez-Rojas JM, Hernández-Damián J, et al. The role of PI3K/AKT/mTOR pathway in the modulation of autophagy and the clearance of protein aggregates in neurodegeneration. Cell Signal. 2014; 26(12):2694- 2701.
[11] Hsia HE, Kumar R, Luca R, et al. Ubiquitin E3 ligase Nedd4-1 acts as a downstream target of PI3K/PTEN-mTORC1 signaling to promote neurite growth. Proc Natl Acad Sci U S A. 2014;111(36): 13205-13210.
[12] Imanaka M, Iida K, Murawaki A, et al. Growth hormone stimulates mechano growth factor expression and activates myoblast transformation in C2C12 cells. Kobe J Med Sci. 2008;54(1):E46-54.
[13] Deng M, Liu P, Xiao H, et al. Improving the osteogenic efficacy of BMP2 with mechano growth factor by regulating the signaling events in BMP pathway. Cell Tissue Res. 2015;361(3):723-731.
[14] Shang J, Fan X, Liu H. The role of mechano-growth factor E peptide in the regulation of osteosarcoma. Oncol Lett. 2015;10(2):697-704.
[15] Yu C, Sha Y, Guo P, et al. Study on the regulatory effects of mechano growth factor on soft tissue repair. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2015; 32(1):235-239.
[16] Stavropoulou A, Halapas A, Sourla A, et al. IGF-1 expression in infarcted myocardium and MGF E peptide actions in rat cardiomyocytes in vitro. Mol Med. 2009;15(5-6):127-135.
[17] Thevis M, Thomas A, Geyer H, et al. Mass spectrometric characterization of a biotechnologically produced full-length mechano growth factor (MGF) relevant for doping controls. Growth Horm IGF Res. 2014;24(6):276-280.
[18] Yang SY, Goldspink G. Different roles of the IGF-I Ec peptide (MGF) and mature IGF-I in myoblast proliferation and differentiation. FEBS Lett. 2002;522 (1-3):156-160.
[19] Zhu SB, Zhu J, Zhou ZZ, et al. TGF-β1 induces human aortic vascular smooth muscle cell phenotype switch through PI3K/AKT/ID2 signaling. Am J Transl Res. 2015;7(12):2764-2774.
[20] Tong Y, Feng W, Wu Y, et al. Mechano-growth factor accelerates the proliferation and osteogenic differentiation of rabbit mesenchymal stem cells through the PI3K/AKT pathway. BMC Biochem. 2015; 16:1.
[21] Peña JR, Pinney JR, Ayala P, et al. Localized delivery of mechano-growth factor E-domain peptide via polymeric microstructures improves cardiac function following myocardial infarction. Biomaterials. 2015; 46:26-34.
[22] Luo Q, Wu K, Zhang B, et al. Mechano growth factor E peptide promotes rat bone marrow-derived mesenchymal stem cell migration through CXCR4-ERK1/2. Growth Factors. 2015;33(3): 210-219.
[23] Malo MS. A High Level of Intestinal Alkaline Phosphatase Is Protective Against Type 2 Diabetes Mellitus Irrespective of Obesity. EBioMedicine. 2015; 2(12):2016-2023.
[24] Delli Mauri A, Petrini M, Vitale D, et al. Alkaline phosphatase level in gingival crevicular fluid during treatment with Quad-Helix. J Biol Regul Homeost Agents. 2015;29(4):1017-1023.
[25] Pabis A, Kamerlin SC. Promiscuity and electrostatic flexibility in the alkaline phosphatase superfamily. Curr Opin Struct Biol. 2016;37:14-21.
[26] Bobeck EA, Hellestad EM, Helvig CF, et al. Oral antibodies to human intestinal alkaline phosphatase reduce dietary phytate phosphate bioavailability in the presence of dietary 1α-hydroxycholecalciferol. Poult Sci. 2016;95(3):570-580.
[27] Millán JL, Whyte MP. Alkaline Phosphatase and Hypophosphatasia. Calcif Tissue Int. 2016;98(4): 398-416.
[28] Khan AR, Awan FR, Najam SS, et al. Elevated serum level of human alkaline phosphatase in obesity. J Pak Med Assoc. 2015;65(11):1182-1185.
[29] Mruthyunjaya S, Rumma M, Ravibhushan G, et al. c-Jun/AP-1 transcription factor regulates laminin-1-induced neurite outgrowth in human bone marrow mesenchymal stem cells: role of multiple signaling pathways. FEBS Lett. 2011;585(12): 1915-1922.
[30] Olivares-Navarrete R, Hyzy SL, Berg ME, et al. Osteoblast lineage cells can discriminate microscale topographic features on titanium-aluminum-vanadium surfaces. Ann Biomed Eng. 2014;42(12):2551-2561.
[31] Feng HW, Tian YD, Zhang HP, et al. Bone Age and Serum Osteocalcin Levels in Children With Obstructive Sleep Apnea Hypopnea Syndrome Before and After Adenotonsillectomy. Am J Ther. 2015. in press.
[32] Inaba N, Sato T, Yamashita T. Low-Dose Daily Intake of Vitamin K2 (Menaquinone-7) Improves Osteocalcin γ-Carboxylation: A Double-Blind, Randomized Controlled Trials. J Nutr Sci Vitaminol (Tokyo). 2015; 61(6):471-480.
[33] Liu J, Yang J. Uncarboxylated osteocalcin inhibits high glucose-induced ROS production and stimulates osteoblastic differentiation by preventing the activation of PI3K/Akt in MC3T3-E1 cells. Int J Mol Med. 2016; 37(1):173-181.
[34] Kim KM, Lim S, Moon JH, et al. Lower uncarboxylated osteocalcin and higher sclerostin levels are significantly associated with coronary artery disease. Bone. 2016;83:178-183.
[35] Yun SH, Kim MJ, Choi BH, et al. Low Level of Osteocalcin Is Related With Arterial Stiffness in Korean Adults: An Inverse J-Shaped Relationship. J Clin Endocrinol Metab. 2016;101(1):96-102.
[36] Park JE, Seo YK, Yoon HH, et al. Electromagnetic fields induce neural differentiation of human bone marrow derived mesenchymal stem cells via ROS mediated EGFR activation. Neurochem Int. 2013; 62(4):418-424.
[37] Bador KM, Wee LD, Halim SA, et al. Serum osteocalcin in subjects with metabolic syndrome and central obesity. Diabetes Metab Syndr. 2015. in press.
[38] Ho MH, Yao CJ, Liao MH, et al. Chitosan nanofiber scaffold improves bone healing via stimulating trabecular bone production due to upregulation of the Runx2/osteocalcin/alkaline phosphatase signaling pathway. Int J Nanomedicine. 2015;10:5941-5954.
[39] Zwakenberg SR, Gundberg CM, Spijkerman AM, et al. Osteocalcin Is Not Associated with the Risk of Type 2 Diabetes: Findings from the EPIC-NL Study. PLoS One. 2015;10(9):e0138693.
[40] Arya N, Moonarmart W, Cheewamongkolnimit N, et al. Osteocalcin and bone-specific alkaline phosphatase in Asian elephants (Elephas maximus) at different ages. Vet J. 2015;206(2):239-240.
[41] Levinger I, Lin X, Zhang X, et al. The effects of muscle contraction and recombinant osteocalcin on insulin sensitivity ex vivo. Osteoporos Int. 2016;27(2): 653-663.
[42] Ling Y, Gao X, Lin H, et al. A common polymorphism rs1800247 in osteocalcin gene was associated with serum osteocalcin levels, bone mineral density, and fracture: the Shanghai Changfeng Study. Osteoporos Int. 2016;27(2):769-779.
[43] Martins AF, Souza PO, Rege IC, et al. Glucocorticoids, calcitonin, and osteocalcin cannot differentiate between aggressive and nonaggressive central giant cell lesions of the jaws. Oral Surg Oral Med Oral Pathol Oral Radiol. 2015;120(3):386-395.
[44] Peura M, Bizik J, Salmenperä P, et al. Bone marrow mesenchymal stem cells undergo nemosis and induce keratinocyte wound healing utilizing the HGF/c-Met/ PI3K pathway. Wound Repair Regen. 2009;17(4): 569-577.
[45] Wang L, Zhang L, Shen W, et al. High expression of VEGF and PI3K in glioma stem cells provides new criteria for the grading of gliomas. Exp Ther Med. 2016;11(2):571-576.
[46] Abliz A, Deng W, Sun R, et al. Wortmannin, PI3K/Akt signaling pathway inhibitor, attenuates thyroid injury associated with severe acute pancreatitis in rats. Int J Clin Exp Pathol. 2015;8(11):13821-13833.
[47] Robbins HL, Hague A. The PI3K/Akt Pathway in Tumors of Endocrine Tissues. Front Endocrinol (Lausanne). 2016;6:188.
[48] Ma LI, Chang Y, Yu L, et al. Pro-apoptotic and anti-proliferative effects of mitofusin-2 via PI3K/Akt signaling in breast cancer cells. Oncol Lett. 2015; 10(6):3816-3822.
[49] Sledd J, Wu D, Ahrens R, et al. Loss of IL-4Rα-mediated PI3K signaling accelerates the progression of IgE/mast cell-mediated reactions. Immun Inflamm Dis. 2015;3(4):420-430.
[50] Zhao J, Li L, Peng L. MAPK1 up-regulates the expression of MALAT1 to promote the proliferation of cardiomyocytes through PI3K/AKT signaling pathway. Int J Clin Exp Pathol. 2015;8(12):15947-15953.
[51] Li XJ, Luo Q, Sun L, et al. The effects of curcumin on PTEN/PI3K/Akt pathway in Ec109 cells. Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2015;31(5):465-468.
[52] Zhang P, Zhang L, Zhu L, et al. The change tendency of PI3K/Akt pathway after spinal cord injury. Am J Transl Res. 2015;7(11):2223-2232.
[53] Lee JJ, Loh K, Yap YS. PI3K/Akt/mTOR inhibitors in breast cancer. Cancer Biol Med. 2015;12(4):342-354.
[54] Chen X, Li YY, Zhang WQ, et al. House dust mite extract induces growth factor expression in nasal mucosa by activating the PI3K/Akt/HIF-1α pathway. Biochem Biophys Res Commun. 2016;469(4): 1055-1061.
[55] Rice GB, Wadhwani NR. PI3K/AKT Pathway and Brain Malformations. Pediatr Neurol Briefs. 2015;29(7):52.
[56] Wang G, Li X, Wang H, et al. Later phase cardioprotection of ischemic post-conditioning against ischemia/reperfusion injury depends on iNOS and PI3K-Akt pathway. Am J Transl Res. 2015;7(12): 2603-2611.
[57] Mayer IA. Clinical Implications of Mutations in the PI3K Pathway in HER2+ Breast Cancer: Prognostic or Predictive? Curr Breast Cancer Rep. 2015;7(4): 210-214.
[58] Sun Y, Tu Y, He LI, et al. High mobility group box 1 regulates tumor metastasis in cutaneous squamous cell carcinoma via the PI3K/AKT and MAPK signaling pathways. Oncol Lett. 2016;11(1):59-62.
[59] Milingos DS, Philippou A, Armakolas A, et al. Insulinlike growth factor-1Ec (MGF) expression in eutopic and ectopic endometrium: characterization of the MGF E-peptide actions in vitro. Mol Med. 2011; 17(1-2):21-28.
[60] Philippou A, Papageorgiou E, Bogdanis G, et al. Expression of IGF-1 isoforms after exercise-induced muscle damage in humans: characterization of the MGF E peptide actions in vitro. In Vivo. 2009;23(4): 567-575.
[61] Qin LL, Li XK, Xu J, et al. Mechano growth factor (MGF) promotes proliferation and inhibits differentiation of porcine satellite cells (PSCs) by down-regulation of key myogenic transcriptional factors. Mol Cell Biochem. 2012;370(1-2):221-230.