Yıl 2019, Cilt 13 , Sayı 3, Sayfalar 183 - 192 2019-12-31

Effect of mesenchymal stem cells and their niche on diabetic and osteoporotic wound healing following osteogenic differentiation and bone matrix formation in vitro

Müge KARAKAYALI [1] , Tuna ÖNAL [2] , Mehmet İbrahim TUĞLU [3]


Objectives: Mesenchymal stem cells (MSC) and their secreted factors (i.e. niche) are becoming growingly popular in bone regeneration. The mechanisms of this effect can be investigated through in vitro models which are cost-effective methods used for determining the effectiveness of new products in experimental and clinical applications. In the present study, we established an experimental diabetic osteoporosis model in a high-glucose culture medium with no estrogen supplement to investigate the effect of MSC and their niche which their factors secreted into 24 hours medium on osteoblastic differentiation, formation of bone islets, and the wound healing model induced by scratch assay. Methods: A culture medium of adipose-derived rat MSC (ADMSC) with no estrogen supplement was used for cell growth to assess osteoblastic differentiation and bone islet formation. A wound model was induced using the scratch assay to investigate the effect of the model on the parameters of wound healing. Cell growth and viability was assessed using MTT assay, cell migration and differentiation and the amount of wound closure were assessed based on the expression of CD44, CD45, and CD73, and osteoblast differentiation was evaluated using Alizarin Red S and von Kossa staining. Morphological observations were performed using an inverted phase-contrast microscope and h-score was assessed with immunohistochemical staining. Results: The use of osteogenic medium with estrogen supplement led to MSC growth and migration as well as bone islet formation. The use of a high-glucose medium without estrogen supplement inhibited MSC differentiation and bone islet formation. The administration of MSC and niche promoted the wound healing initiated by the administration of the scratch assay and this promotion was significant in terms of all the parameters of wound healing. Conclusion: The results indicated that the therapeutic effect of MSC and niche could be used as an effective treatment model in wound healing in patients with diabetic osteoporosis. Moreover, this model could be a cost-effective method for the new treatment products to be applied in dental and orthopedic practice prior to animal experiments and clinical trials.
diabetic osteoporosis, in vitro, mesenchymal stem cell, niche, osteoblastic differentiation
  • 1. Squillaro T, Peluso G, Galderisi U. Clinical trials with mesenchymal stem cells: an update. Cell Transplant 2016;25:829–48. 2. Garg P, Mazur MM, Buck AC, Wandtke ME, Liu J, Ebraheim NA. Preospective review of mesenchymal stem cells differentiation into osteoblasts. Orthop Surg 2017;9:13–9. 3. Wu ZY, Sun Q, Liu M, Grottkau BE, He ZX, Zou Q, Ye C. Correlation between the efficacy of stem cell therapy for osteonecrosis of the femoral head and cell viability. BMC Musculoskelet Disord 2020;21:55. 4. Ciuffreda MC, Malpasso G, Musarò P, Turco V, Gnecchi M. Protocols for in vitro differentiation of human mesenchymal stem cells into osteogenic, chondrogenic and adipogenic lineages. Methods Mol Biol 2016;1416:149–58. 5. Hauzeur JP, De Maertelaer V, Baudoux E, Malaise M, Beguin Y, Gangji V. Inefficacy of autologous bone marrow concentrate in stage three osteonecrosis: a randomized controlled double-blind trial. Int Orthop 2018;42:1429–35. 6. Cheng C, Wentworth K, Shoback DM. New frontiers in osteoporosis therapy. Annu Rev Med 2020;71:277–88. 7. Murray CE, Coleman CM. Impact of diabetes mellitus on bone health. Int J Mol Sci 2019;20:19. 8. Rathinavelu S, Guidry-Elizondo C, Banu J. Molecular modulation of osteoblasts and osteoclasts in type 2 diabetes. J Diabetes Res 2018; 2018:6354787. 9. Karaöz E, Aksoy A, Ayhan S, Sariboyaci AE, Kaymaz F, Kasap M. Characterization of mesenchymal stem cells from rat bone marrow: ultrastructural properties, differentiation potential and immunophenotypic markers. Histochem Cell Biol 2009;132:533–46. 10. Karaöz E, Do¤an BN, Aksoy A, Gacar G, Akyüz S, Ayhan S, Genç ZS, Yürüker S, Duruksu G, Demircan PC, Sariboyaci AE. Isolation and in vitro characterisation of dental pulp stem cells from natal teeth. Histochem Cell Biol 2010;133:95–112. 11. Karaöz E, Okçu A, Gacar G, Sa¤lam O, Yürüker S, Kenar H. A comprehensive characterization study of human bone marrow mscs with an emphasis on molecular and ultrastructural properties. J Cell Physiol 2011;226:1367–82. 12. Çelebi B, Elçin YM. Proteome analysis of rat bone marrow mesenchymal stem cell subcultures. J Proteome Res 2009;8:2164–72. 13. Michael S, Achilleos C, Panayiotou T, Strati K. Inflammation shapes stem cells and stemness during infection and beyond. Front Cell Dev Biol 2016;4:118. 14. A¤acayak S, Gülsün B, Karaoz E, Nergiz Y, Uçan MC. Effects of mesenchymal stem cells in critical size bone defect. Eur Rev Med Pharmacol Sci 2012;16:679–86. 15. Huang KC, Chuang PY, Yang TY, Huang TW, Chang SF. Hyperglycemia inhibits osteoblastogenesis of rat bone marrow stromal cells via activation of the Notch2 signaling pathway. Int J Med Sci 2019;16:696–703. 16. Jiang H, Wang Y, Meng J, Chen S, Wang J, Qiu Y, Zhao J, Guo T. Effects of transplanting bone marrow stromal cells transfected with CXCL13 on fracture healing of diabetic rats. Cell Physiol Biochem 2018;49:123–33. 17. Maycas M, Portolés MT, Matesanz MC, Buendía I, Linares J, Feito MJ, Arcos D, Vallet-Regí M, Plotkin LI, Esbrit P, Gortázar AR. High glucose alters the secretome of mechanically stimulated osteocyte- like cells affecting osteoclast precursor recruitment and differentiation. J Cell Physiol 2017;232:3611–21. 18. Deng X, Xu M, Shen M, Cheng J. Effects of type 2 diabetic serum on proliferation and osteogenic differentiation of mesenchymal stem cells. J Diabetes Res 2018;5765478. 19. Qu B, Gong K, Yang HS, Li YG, Jiang T, Zeng ZM, Cao ZR, Pan XM. MiR-449 overexpression inhibits osteogenic differentiation of bone marrow mesenchymal stem cells via suppressing Sirt1/Fra-1 pathway in high glucose and free fatty acids microenvironment. Biochem Biophys Res Commun 2018;496:120–6. 20. Saito A, Nagaishi K, Iba K, Mizue Y, Chikenji T, Otani M, Nakano M, Oyama K, Yamashita T, Fujimiya M. Umbilical cord extracts improve osteoporotic abnormalities of bone marrow-derived mesenchymal stem cells and promote their therapeutic effects on ovariectomised rats. Sci Rep 2018;8:1161. 21. Zhang M, Li Y, Rao P, Huang K, Luo D, Cai X, Xiao J. Blockade of receptors of advanced glycation end products ameliorates diabetic osteogenesis of adipose-derived stem cells through DNA methylation and Wnt signalling pathway. Cell Prolif 2018;51:e12471. 22. Xie H, Wang Q, Zhang X, Wang T, Hu W, Manicum T, Chen H, Sun L. Possible therapeutic potential of berberine in the treatment of STZ plus HFD-induced diabetic osteoporosis. Biomed Pharmacother 2018;108:280–7. 23. Ding X, Yang L, Hu Y, Yu J, Tang Y, Luo D, Zheng L. Effect of local application of biphosphonates on improving peri-implant osseointegration in type-2 diabetic osteoporosis. Am J Transl Res 2019;11: 5417–37. 24. Chen Y, Hu Y, Yang L, Zhou J, Tang Y, Zheng L, Qin P. Runx2 alleviates high glucose-suppressed osteogenic differentiation via PI3K/AKT/GSK3‚/μ-catenin pathway. Cell Biol Int 2017;41:822– 32. 25. Zavatti M, Guida M, Maraldi T, Beretti, F, Bertoni L, La Sala GB, De Pol A. Estrogen receptor signaling in the ferutinin-induced osteoblastic differentiation of human amniotic fluid stem cells. Life Sci 2016;164:15–22. 26. Crescitelli MC, Rauschemberger MB, Cepeda S, Sandoval M, Massheimer VL. Role of estrone on the regulation of osteoblastogenesis. Mol Cell Endocrinol 2019;498:110582 27. Gavali S, Gupta MK, Daswani B, Wani MR, Sirdeshmukh R, Khatkhatay MI. Estrogen enhances human osteoblast survival and function via promotion of autophagy. Biochim Biophys Acta Mol Cell Res 2019;1866:1498–507. 28. Sun LJ, Li C, Wen XH, Guo L, Guo ZF, Liao LQ, Guo Y. Icariin stimulates hFOB 1.19 osteoblast proliferation and differentiation via OPG/RANKL mediated by the estrogen receptor. Curr Pharm Biotechnol 2020. doi: 10.2174/1389201021666200123102550. [Epub ahead of print]. 29. Lv H, Sun Y, Zhang Y. MiR-133 is involved in estrogen deficiencyinduced osteoporosis through modulating osteogenic differentiation of mesenchymal stem cells. Med Sci Monit 2015;27:1527–34. 30. Deliloglu-Gurhan I, Tuglu I, Vatansever HS, Ozdal-Kurt F, Ekren H, Taylan M, Sen BH. The effect of osteogenic medium on the adhesion of rat bone marrow stromal cell to the hydroxyapatite. Saudi Med J 2006;27:305–11. 31. Deliloglu-Gurhan SI, Vatansever HS, Ozdal-Kurt F, Tuglu I. Characterization of osteoblasts derived from bone marrow stromal cells in a modified cell culture system. Acta Histochem 2006;108:49– 57. 32. Yuksel S, Guleç MA, Gultekin MZ, Adan›r O, Caglar A, Beytemur O, Onur Küçüky›ld›r›m B, Avc› A, Subafl› C, ‹nci Ç, Karaoz E. Comparison of the early period effects of bone marrow-derived mesenchymal stem cells and platelet-rich plasma on the Achilles tendon ruptures in rats. Connect Tissue Res 2016;57:360–73. 33. Özdal-Kurt F, Tu¤lu I, Vatansever HS, Tong S, fien BH, Delilo¤lu- Gürhan SI. The effect of different implant biomaterials on the behavior of canine bone marrow stromal cells during their differentiation into osteoblasts. Biotech Histochem 2016;91:412–22. 34. Özdal-Kurt F, Tu¤lu I, Vatansever HS, Tong S, Delilo¤lu-Gürhan SI. The effect of autologous bone marrow stromal cells differentiated on scaffolds for canine tibial bone reconstruction. Biotech Histochem 2015;90:516–28. 35. Jin E, Kim TH, Han S, Kim SW. Amniotic epithelial cells promote wound healing in mice through high epithelialization and engraftment. J Tissue Eng Regen Med 2016;10:613–22. 36. Sharma M, Sahu K, Singh SP, Jain B. Wound healing activity of curcumin conjugated to hyaluronic acid: in vitro and in vivo evaluation. Artif Cells Nanomed Biotechnol 2018;46:1009–17. 37. Paschou SA, Dede AD, Anagnostis PG, Vryonidou A, Morganstein D, Goulis DG. Type 2 diabetes and osteoporosis: a guide to optimal management. J Clin Endocrinol Metab 2017;102:3621–34. 38. Gadelkarim M, Abushouk AI, Ghanem E, Hamaad AM, Saad AM, Abdel-Daim MM. Adipose-derived stem cells: effectiveness and advances in delivery in diabetic wound healing. Biomed Pharmacother 2018;107:625–33. 39. Li LY, Wang XL, Wang GS, Zhao HY. MiR-373 promotes the osteogenic differentiation of BMSCs from the estrogen deficiency induced osteoporosis. Eur Rev Med Pharmacol Sci 2019;23:7247–55. 40. Ceylan H, Balc›k OS, Güler MO, Kocabey S, Tekinay AB, Ünal Gülsüner H. Bone-like mineral nucleating peptide nanofibers induce differentiation of human mesenchymal stem cells into mature osteoblasts. Biomacromolecules 2014;15:2407–18. 41. Yang C, Wang Y, Xu H. Correction: Fluoride regulate osteoblastic transforming growth factor-β1 signaling by mediating recycling of the Type I eeceptor ALK5. PLoS One 2017;12:e0170674. 42. Chen S, Yi B, Su LB, Zhang YR, Chen CL. In vitro evaluation of a novel osteo-inductive scaffold for osteogenic differentiation of bonemarrow mesenchymal stem cells. J Craniofac Surg 2020;31:577–82. 43. Ching HS, Luddin N, Rahman IA, Ponnuraj KT. Expression of odontogenic and osteogenic markers in DPSCs and SHED: a review. Curr Stem Cell Res Ther 2017;12:71–9. 44. Kuyucu U, Alpa¤at fi, Bender OM, ‹lkerli E, Köstem fi‹, Güler NT. Kemik yap›s› ve kemik metabolizmas›nda osteoprotegerin, RANKL ve RANK iliflkisi. Ankara: Türkiye Endokrinoloji ve Metabolizma Derne¤i ve Baflkent Üniversitesi T›p Fakültesi; 2010. 45. Lee SH, Oh KN, Han Y, Choi YH, Lee KY. Estrogen receptor · regulates Dlx3-mediated osteoblast differentiation. Mol Cells 2016; 39:156–62. 46. Nielsen FM, Riis SE, Andersen JI, Lesage R, Fink, T, Pennisi, CP, Zachar V. Discrete adipose-derived stem cell subpopulations may display differential functionality after in vitro expansion despite convergence to a common phenotype distribution. Stem Cell Res Ther 2016;7:177. 47. Menéndez-Menéndez Y, Otero-Hernández J, Vega JA, Pérez- Basterrechea M, Pérez-López S, Álvarez-Viejo M, Ferrero- Gutiérrez A. The role of bone marrow mononuclear cell-conditioned medium in the proliferation and migration of human dermal fibroblasts. Cell Mol Biol Lett 2017;22:29. 48. Kruse CR, Singh M, Sørensen JA, Eriksson E, Nuutila K. The effect of local hyperglycemia on skin cells in vitro and on wound healing in euglycemic rats. J Surg Res 2016;206:418–26. 49. di Martino O, Tito A, De Lucia A, Cimmino A, Cicotti F, Apone F, Colucci G, Calabrò V. Hibiscus syriacus extract from an established cell culture stimulates skin wound healing. Biomed Res Int 2017;2017:7932019. 50. Kato H, Taguchi Y, Tominaga K, Kimura D, Yamawaki I, Noguchi M, Yamauchi N, Tamura I, Tanaka A, Umeda M. High glucose concentrations suppress the proliferation of human periodontal ligament stem cells and their differentiation into osteoblasts. J Periodontol 2016;87:e44–51. 51. Zong S, Zeng G, Fang Y, Peng J, Zou B, Gao T, Zhao J. The effects of α-zearalanol on the proliferation of bone-marrow-derived mesenchymal stem cells and their differentiation into osteoblasts. J Bone Miner Metabob 2016;34:151–60. 52. Huang KC, Chuang PY, Yang TY, Huang TW, Chang SF. Hyperglycemia inhibits osteoblastogenesis of rat bone marrow stromal cells via activation of the Notch2 signaling pathway. Int J Med Sci 2019;16:696–703.
Birincil Dil en
Konular Sağlık Bilimleri ve Hizmetleri
Bölüm Original Articles
Yazarlar

Yazar: Müge KARAKAYALI (Sorumlu Yazar)
Kurum: IZMIR DEMOCRACY UNIVERSITY
Ülke: Turkey


Yazar: Tuna ÖNAL
Kurum: MANISA CELAL BAYAR UNIVERSITY
Ülke: Turkey


Yazar: Mehmet İbrahim TUĞLU
Kurum: MANISA CELAL BAYAR UNIVERSITY
Ülke: Turkey


Tarihler

Yayımlanma Tarihi : 31 Aralık 2019

Bibtex @araştırma makalesi { anatomy716517, journal = {Anatomy}, issn = {1307-8798}, eissn = {1308-8459}, address = {}, publisher = {Türk Anatomi ve Klinik Anatomi Derneği}, year = {2019}, volume = {13}, pages = {183 - 192}, doi = {}, title = {Effect of mesenchymal stem cells and their niche on diabetic and osteoporotic wound healing following osteogenic differentiation and bone matrix formation in vitro}, key = {cite}, author = {KARAKAYALI, Müge and ÖNAL, Tuna and TUĞLU, Mehmet İbrahim} }
APA KARAKAYALI, M , ÖNAL, T , TUĞLU, M . (2019). Effect of mesenchymal stem cells and their niche on diabetic and osteoporotic wound healing following osteogenic differentiation and bone matrix formation in vitro. Anatomy , 13 (3) , 183-192 . Retrieved from https://dergipark.org.tr/tr/pub/anatomy/issue/53646/716517
MLA KARAKAYALI, M , ÖNAL, T , TUĞLU, M . "Effect of mesenchymal stem cells and their niche on diabetic and osteoporotic wound healing following osteogenic differentiation and bone matrix formation in vitro". Anatomy 13 (2019 ): 183-192 <https://dergipark.org.tr/tr/pub/anatomy/issue/53646/716517>
Chicago KARAKAYALI, M , ÖNAL, T , TUĞLU, M . "Effect of mesenchymal stem cells and their niche on diabetic and osteoporotic wound healing following osteogenic differentiation and bone matrix formation in vitro". Anatomy 13 (2019 ): 183-192
RIS TY - JOUR T1 - Effect of mesenchymal stem cells and their niche on diabetic and osteoporotic wound healing following osteogenic differentiation and bone matrix formation in vitro AU - Müge KARAKAYALI , Tuna ÖNAL , Mehmet İbrahim TUĞLU Y1 - 2019 PY - 2019 N1 - DO - T2 - Anatomy JF - Journal JO - JOR SP - 183 EP - 192 VL - 13 IS - 3 SN - 1307-8798-1308-8459 M3 - UR - Y2 - 2019 ER -
EndNote %0 Anatomy Effect of mesenchymal stem cells and their niche on diabetic and osteoporotic wound healing following osteogenic differentiation and bone matrix formation in vitro %A Müge KARAKAYALI , Tuna ÖNAL , Mehmet İbrahim TUĞLU %T Effect of mesenchymal stem cells and their niche on diabetic and osteoporotic wound healing following osteogenic differentiation and bone matrix formation in vitro %D 2019 %J Anatomy %P 1307-8798-1308-8459 %V 13 %N 3 %R %U
ISNAD KARAKAYALI, Müge , ÖNAL, Tuna , TUĞLU, Mehmet İbrahim . "Effect of mesenchymal stem cells and their niche on diabetic and osteoporotic wound healing following osteogenic differentiation and bone matrix formation in vitro". Anatomy 13 / 3 (Aralık 2020): 183-192 .
AMA KARAKAYALI M , ÖNAL T , TUĞLU M . Effect of mesenchymal stem cells and their niche on diabetic and osteoporotic wound healing following osteogenic differentiation and bone matrix formation in vitro. Anatomy. 2019; 13(3): 183-192.
Vancouver KARAKAYALI M , ÖNAL T , TUĞLU M . Effect of mesenchymal stem cells and their niche on diabetic and osteoporotic wound healing following osteogenic differentiation and bone matrix formation in vitro. Anatomy. 2019; 13(3): 192-183.