Iranian
Biomedical Journal
Volume 26, Issue 6 (11-2022)
IBJ 2022, 26(6): 463-474 |
Back to browse issues page
Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
Ahmadi A, Ebadi S S, Tayebi T, Ebadi S A, Sarzaeem M M, Niknejad H. Osteogenic Differentiation Effect of BMP-9 with Phenamil and Simvastatin on Intact Human Amniotic Epithelial Stem Cells. IBJ 2022; 26 (6) :463-474
URL: http://ibj.pasteur.ac.ir/article-1-3748-en.html
URL: http://ibj.pasteur.ac.ir/article-1-3748-en.html
Armin Ahmadi 
, Seyed Shayan Ebadi , Tahereh Tayebi , Seyed Alireza Ebadi , Mohammad Mahdi Sarzaeem , Hassan Niknejad *
, Seyed Shayan Ebadi , Tahereh Tayebi , Seyed Alireza Ebadi , Mohammad Mahdi Sarzaeem , Hassan Niknejad *
Abstract:
Background: Bone tissue engineering has shown to be a promising strategy for repairing bone defects without causing harmful side effects to the patient. Three main building blocks of tissue engineering, including seeding cells, scaffold, and signaling molecules, are required for adequate bone regeneration. The human amniotic membrane (hAM) is the innermost of the placental membranes. In addition to providing a source of stem cells and growth factors, hAM has several features that make it an appropriate scaffold containing stem cells for use in tissue engineering purposes. The present investigation aimed to assess the effect of bone morphogenetic protein-9 (BMP-9) combined with phenamil and simvastatin on osteogenic induction of hAM with its human amniotic membrane epithelial cells (hAECs).
Methods: Using six different osteogenic medium (OMs), we cultured hAM for 14 days. The basic OMs were chosen as the first group and other media were made by adding BMP-9, phenamil, simvastatin, BMP-9 alongside phenamil, and BMP-9 alongside simvastatin to the basic OMs. Finally, viability assay, tissue mineralization, calcium and phosphate content determination, and measurement of lactic acid dehydrogenase (LDH), and alkaline phosphatase (ALP) activity were performed.
Results: Among all study groups, groups containing simvastatin showed a significantly lower level of viability. Although all media could induce osteogenic features, the hAECs cultured in media containing BMP-9 and phenamil demonstrated a wider area of mineralization and a significantly higher level of calcium and phosphate content, LDH, and ALP activity.
Conclusion: Our findings indicated that the use of phenamil together with BMP-9 could synergistically show in situ osteogenic induction in hAECs, which could be a new insight into translational medicine.
Methods: Using six different osteogenic medium (OMs), we cultured hAM for 14 days. The basic OMs were chosen as the first group and other media were made by adding BMP-9, phenamil, simvastatin, BMP-9 alongside phenamil, and BMP-9 alongside simvastatin to the basic OMs. Finally, viability assay, tissue mineralization, calcium and phosphate content determination, and measurement of lactic acid dehydrogenase (LDH), and alkaline phosphatase (ALP) activity were performed.
Results: Among all study groups, groups containing simvastatin showed a significantly lower level of viability. Although all media could induce osteogenic features, the hAECs cultured in media containing BMP-9 and phenamil demonstrated a wider area of mineralization and a significantly higher level of calcium and phosphate content, LDH, and ALP activity.
Conclusion: Our findings indicated that the use of phenamil together with BMP-9 could synergistically show in situ osteogenic induction in hAECs, which could be a new insight into translational medicine.
Type of Study: Full Length/Original Article |
Subject:
Tissue Engineering and Cell Biology
References
1. Zhang C, Yu L, Liu S, Wang Y. Human amnion-derived mesenchymal stem cells promote osteogenic and angiogenic differentiation of human adipose-derived stem cells. PloS one 2017; 12(10): e0186253. [DOI:10.1371/journal.pone.0186253]
2. 2. Wang JJ, Ye F, Cheng LJ, Shi YJ, Bao J, Sun HQ, Wang W, Zhang P, Bu H. Osteogenic differentiation of mesenchymal stem cells promoted by overexpression of connective tissue growth factor. Journal of zhejiang university science B 2009; 10(5): 355-367. [DOI:10.1631/jzus.B0820252]
3. Azevedo HS, Pashkuleva I. Biomimetic supramolecular designs for the controlled release of growth factors in bone regeneration. Advanced drug delivery reviews 2015; 94: 63-76. [DOI:10.1016/j.addr.2015.08.003]
4. Sánchez-Duffhues G, Hiepen C, Knaus P, Ten Dijke P. Bone morphogenetic protein signaling in bone homeostasis. Bone 2015; 80: 43-59. [DOI:10.1016/j.bone.2015.05.025]
5. Beederman M, Lamplot JD, Nan G, Wang J, Liu X, Yin L, Li R, Shui W, Zhang H, Kim SH, Zhang W, Zhang J, Kong Y, Denduluri S, Rose Rogers M, Pratt A, Haydon RC, Luu HH, Angeles J, Shi LL, He TC. BMP signaling in mesenchymal stem cell differentiation and bone formation. Journal of biomedical science and engineering 2013; 6(8A): 32. [DOI:10.4236/jbise.2013.68A1004]
6. Bharadwaz A, Jayasuriya AC. Osteogenic differentiation cues of the bone morphogenetic protein-9 (BMP-9) and its recent advances in bone tissue regeneration. Materials science and engineering: C 2021; 120: 111748. [DOI:10.1016/j.msec.2020.111748]
7. Wu JQ, Mao LB, Liu LF, Li YM, Wu J, Yao J, Zhang F-H, Liu T-U, Yuan L. Identification of key genes and pathways of BMP-9-induced osteogenic differentiation of mesenchymal stem cells by integrated bioinformatics analysis. Journal of orthopaedic surgery and research 2021; 16(1): 273. [DOI:10.1186/s13018-021-02390-w]
8. Wang Y, Zhu G, Li N, Song J, Wang L, Shi X. Small molecules and their controlled release that induce the osteogenic/chondrogenic commitment of stem cells. Biotechnology advances 2015; 33(8): 1626-1640. [DOI:10.1016/j.biotechadv.2015.08.005]
9. Wang Y, Xia C, Chen Y, Jiang T, Hu Y, Gao Y. Resveratrol synergistically promotes BMP9-induced osteogenic differentiation of mesenchymal stem cells. Stem cells international 2022; 2022: 8124085. [DOI:10.1155/2022/8124085]
10. Lo KWH, Kan HM, Laurencin CT. Short-term administration of small molecule phenamil induced a protracted osteogenic effect on osteoblast-like MC3T3-E1 cells. Journal of tissue engineering and regenerative medicine 2016; 10(6): 518-526. [DOI:10.1002/term.1786]
11. Niu J, Ding G, Zhang L. Effects of simvastatin on the osteogenic differentiation and immunomodulation of bone marrow mesenchymal stem cells. Molecular medicine reports 2015; 12(6): 8237-8240. [DOI:10.3892/mmr.2015.4476]
12. Park KW, Waki H, Kim W-K, Davies BS, Young SG, Parhami F, Tontonoz P. The small molecule phenamil induces osteoblast differentiation and mineralization. Molecular and cellular biology 2009; 29(14): 3905-3914. [DOI:10.1128/MCB.00002-09]
13. Ramkumar S, Raghunath A, Raghunath S. Statin therapy: review of safety and potential side effects. Acta cardiologica sinica 2016; 32(6): 631.
14. Qiao LJ, Kang KL, Heo JS. Simvastatin promotes osteogenic differentiation of mouse embryonic stem cells via canonical Wnt/β-catenin signaling. Molecules and cells 2011; 32(5): 437-444. [DOI:10.1007/s10059-011-0107-6]
15. Chamani S, Liberale L, Mobasheri L, Montecucco F, Al-Rasadi K, Jamialahmadi T, Sahebkar A. The role of statins in the differentiation and function of bone cells. European journal of clinical investigation 2021; 51(7): e13534. [DOI:10.1111/eci.13534]
16. Oryan A, Kamali A, Moshiri A. Potential mechanisms and applications of statins on osteogenesis: Current modalities, conflicts and future directions. Journal of controlled release 2015; 215: 12-24. [DOI:10.1016/j.jconrel.2015.07.022]
17. Tehrani FA, Modaresifar K, Azizian S, Niknejad H. Induction of antimicrobial peptides secretion by IL-1β enhances human amniotic membrane for regenerative medicine. Scientific reports 2017; 7(1): 17022. [DOI:10.1038/s41598-017-17210-7]
18. Ghamari SH, Abbasi-Kangevari M, Tayebi T, Bahrami S, Niknejad H. The Bottlenecks in Translating Placenta-Derived Amniotic Epithelial and Mesenchymal Stromal Cells Into the Clinic: Current Discrepancies in Marker Reports. Front bioeng biotechnol 2020; 8: 180. [DOI:10.3389/fbioe.2020.00180]
19. Heckmann N, Auran R, Mirzayan R. Application of Amniotic Tissue in Orthopedic Surgery. American journal of orthopedics 2016; 45(7): e421-e425.
20. Starecki M, Schwartz JA, Grande DA. Evaluation of amniotic-derived membrane biomaterial as an adjunct for repair of critical sized bone defects. Advances in orthopedic surgery 2014; 2014: 572586. [DOI:10.1155/2014/572586]
21. Dziedzic DSM, Francisco JC, Mogharbel BF, Irioda AC, Stricker PEF, Floriano J, Noronha Ld, Abdelwahid E, Regina Cavichiolo Franco C, Athayde Teixeira de Carvalho K. Combined biomaterials: Amniotic membrane and adipose tissue to restore injured bone as promoter of calcification in bone regeneration: Preclinical model. Calcified tissue international 2021; 108(5): 667-679. [DOI:10.1007/s00223-020-00793-1]
22. Lindenmair A, Wolbank S, Stadler G, Meinl A, Peterbauer-Scherb A, Eibl J, Polin H, Gabriel C, van Griensven M, Red H. Osteogenic differentiation of intact human amniotic membrane. Biomaterials 2010; 31(33): 8659-8665. [DOI:10.1016/j.biomaterials.2010.07.090]
23. Luan F, Ma K, Mao J, Yang F, Zhang M, Luan H. Differentiation of human amniotic epithelial cells into osteoblasts is induced by mechanical stretch via the Wnt/β-catenin signalling pathway. Molecular medicine reports 2018; 18(6): 5717-5725. [DOI:10.3892/mmr.2018.9571]
24. Biniazan F, Manzari-Tavakoli A, Safaeinejad F, Moghimi A, Rajaei F, Niknejad H. The differentiation effect of bone morphogenetic protein (BMP) on human amniotic epithelial stem cells to express ectodermal lineage markers. Cell and tissue research 2021; 383(2): 751-763. [DOI:10.1007/s00441-020-03280-z]
25. Sharma U, Pal D, Prasad R. Alkaline phosphatase: an overview. Indian journal of clinical biochemistry 2014; 29(3): 269-278. [DOI:10.1007/s12291-013-0408-y]
26. Nian F, Qian Y, Xu F, Yang M, Wang H, Zhang Z. LDHA promotes osteoblast differentiation through histone lactylation. Biochemical and biophysical research communications 2022; 615: 31-35. [DOI:10.1016/j.bbrc.2022.05.028]
27. Heggebö J, Haasters F, Polzer H, Schwarz C, Saller MM, Mutschler W, Schieker M, Christian Prall W. Aged human mesenchymal stem cells: the duration of bone morphogenetic protein-2 stimulation determines induction or inhibition of osteogenic differentiation. Orthopedic reviews 2014; 6(2): 5242. [DOI:10.4081/or.2014.5242]
28. Vanhatupa S, Ojansivu M, Autio R, Juntunen M, Miettinen S. Bone morphogenetic protein-2 induces donor-dependent osteogenic and adipogenic differentiation in human adipose stem cells. Stem cells translational medicine 2015; 4(12): 1391-1402. [DOI:10.5966/sctm.2015-0042]
29. Aksel H, Huang GT-J. Combined effects of vascular endothelial growth factor and bone morphogenetic protein 2 on odonto/osteogenic differentiation of human dental pulp stem cells in vitro. Journal of endodontics 2017; 43(6): 930-935. [DOI:10.1016/j.joen.2017.01.036]
30. Farhadihosseinabadi B, Farahani M, Tayebi T, Jafari A, Biniazan F, Modaresifar K, Moravvej H, Bahrami S, Redl H, Tayebi L, Niknejad H. Amniotic membrane and its epithelial and mesenchymal stem cells as an appropriate source for skin tissue engineering and regenerative medicine. Artificial cells, nanomedicine, and biotechnology 2018; 46(sup2): 431-440. [DOI:10.1080/21691401.2018.1458730]
31. Tang K, Wu J, Xiong Z, Ji Y, Sun T, Guo X. Human acellular amniotic membrane: a potential osteoinductive biomaterial for bone regeneration. Journal of biomaterials applications 2018; 32(6): 754-764. [DOI:10.1177/0885328217739753]
32. Starecki M, Schwartz JA, Grande DA. Evaluation of amniotic-derived membrane biomaterial as an adjunct for repair of critical sized bone defects. Advances in orthopedic surgery 2014; 2014: 1-5. [DOI:10.1155/2014/572586]
33. Niknejad H, Peirovi H, Jorjani M, Ahmadiani A, Ghanavi J, Seifalian AM. Properties of the amniotic membrane for potential use in tissue engineering. European cells and materials 2008; 15: 88-99. [DOI:10.22203/eCM.v015a07]
34. Li Y, Liu Z, Tang Y, Feng W, Zhao C, Liao J, Zhang C, Chen H, Ren Y, Dong S, Liu Y, Hu N, Huang W. Schnurri-3 regulates BMP9-induced osteogenic differentiation and angiogenesis of human amniotic mesenchymal stem cells through Runx2 and VEGF. Cell death and disease 2020; 11(1): 1-20. [DOI:10.1038/s41419-020-2279-5]
35. Teven CM, Rossi MT, Shenaq DS, Ameer GA, Reid RR. Bone morphogenetic protein-9 effectively induces osteogenic differentiation of reversibly immortalized calvarial mesenchymal progenitor cells. Genes and diseases. 2015; 2(3): 268-275. [DOI:10.1016/j.gendis.2015.06.003]
36. Wang P, Wang Y, Tang W, Wang X, Pang Y, Yang S, Wei Y, Gao H, Wang D, Cao D. Bone morphogenetic protein-9 enhances osteogenic differentiation of human periodontal ligament stem cells via the JNK pathway. PloS one 2017; 12(1): e0169123. [DOI:10.1371/journal.pone.0169123]
37. Yuan C, Gou X, Deng J, Dong Z, Ye P, Hu Z. FAK and BMP-9 synergistically trigger osteogenic differentiation and bone formation of adipose derived stem cells through enhancing Wnt-β-catenin signaling. Biomedicine and pharmacotherapy 2018; 105: 753-757. [DOI:10.1016/j.biopha.2018.04.185]
38. Fan J, Im CS, Cui Z-K, Guo M, Bezouglaia O, Fartash A, Lee J-Y, Nguyen J, Wu BM, Aghaloo T, Lee M. Delivery of phenamil enhances BMP-2-induced osteogenic differentiation of adipose-derived stem cells and bone formation in calvarial defects. Tissue engineering part A 2015; 21(13-14): 2053-2065. [DOI:10.1089/ten.tea.2014.0489]
39. Fan J, Guo M, Im CS, Pi-Anfruns J, Cui Z-K, Kim S, Wu BM, Aghaloo TL, Lee M. Enhanced mandibular bone repair by combined treatment of bone morphogenetic protein 2 and small-molecule phenamil. Tissue engineering part A 2017; 23(5-6): 195-207. [DOI:10.1089/ten.tea.2016.0308]
40. James AW, LaChaud G, Shen J, Asatrian G, Nguyen V, Zhang X, Ting K, Soo C. A review of the clinical side effects of bone morphogenetic protein-2. Tissue egineering part B: Reviews 2016; 22(4): 284-297. [DOI:10.1089/ten.teb.2015.0357]
41. Feng C, Xiao L, Yu J, Li D, Tang T, Liao W, Wang Z-R, Lu AQ. Simvastatin promotes osteogenic differentiation of mesenchymal stem cells in rat model of osteoporosis through BMP-2/Smads signaling pathway. European review for medical and pharmacological sciences 2020; 24(1): 434-443.
42. Zhang M, Bian Y, Tao H, Yang X, Mu W. Simvastatin induces osteogenic differentiation of MSCs via Wnt/β-catenin pathway to promote fracture healing. European review for medical and pharmacological sciences 2018; 22(9): 2896-2905.
43. Zhao Bj, Liu Yh. Simvastatin induces the osteogenic differentiation of human periodontal ligament stem cells. Fundamental and clinical pharmacology 2014; 28(5): 583-592. [DOI:10.1111/fcp.12050]
44. Pagkalos J, Cha JM, Kang Y, Heliotis M, Tsiridis E, Mantalaris A. Simvastatin induces osteogenic differentiation of murine embryonic stem cells. Journal of bone and mineral research 2010; 25(11): 2470-2478. [DOI:10.1002/jbmr.163]
45. Sabandal MMI, Schäfer E, Aed J, Jung S, Kleinheinz J, Sielker S. Simvastatin induces adverse effects on proliferation and mineralization of human primary osteoblasts. Head and face medicine 2020; 16(1): 1-9. [DOI:10.1186/s13005-020-00232-4]
| Rights and permissions | |
 |
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
IBJ is a member of Committee on Publication Ethics (COPE)
and follows its guidelines |
The articles of this journal are licensed under
a Creative Commons Attribution-NonDerivatives 4.0 International License. .png) |
 IBJ is owned and published by Pasteur Institute of Iran |