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Erschienen in:

27.03.2022 | Original Article

Enamel matrix derivative expedites osteogenic differentiation of BMSCs via Wnt/β-catenin pathway in high glucose microenvironment

verfasst von: MaoHua Meng, Qian Xia, Ying Li, Xin Chen, QinYing Wang, JingQiao Chen, XingXing Xu, Huan Wang, JiaYu Shu, Jing Lu, Lu Cheng, ZhaoYang Ye, Bin Song, Qiang Dong

Erschienen in: Journal of Bone and Mineral Metabolism | Ausgabe 3/2022

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Abstract

Introduction

The influence of enamel matrix derivative (EMD) on proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) was explored in high glucose (HG) microenvironment with interaction of Wnt/β-catenin pathway.

Materials and Methods

Extraction of BMSCs from Sprague–Dawley rats, culture, and identification were manifested. The cells were treated with different concentration of EMD in HG to figure out the most available concentration for proliferation and osteogenic differentiation. Then, observation of cell growth curve and cell cycle changes, and detection of Osterix, runt-related transcription factor 2 (Runx2), COL-I, early osteogenic indexes, Calcium salt deposition, and β-catenin protein in Wnt/β-catenin pathway were assured. After adding Wnt/β-catenin pathway inhibitor (XAV-939) in the cells with osteogenesis induction, detection of binding of β-catenin to Osterix was clarified.

Results

Via identification BMSCs cultured in vitro was qualified. Different concentrations of EMD could accelerate cell proliferation in HG and osteogenesis induction, and 75 μg/mL EMD had the best effect. The HG augmented BMSCs proliferation and the propidium iodide index of flow cytometry cycle was elevated in HG, which were strengthened via the EMD. After BMSCs’ osteogenesis induction, Osterix, Runx2, CoL-1, early osteogenic indexes, and calcium salt deposition were reduced, but elevated via EMD. β-Catenin was the lowest in the HG, but elevated after EMD. After addition of XAV-939, reduction of β-catenin and the downstream (Osterix and Runx2) were manifested. Detection of binding protein bands was in β-catenin and Osterix of the HG after EMD treatment.

Conclusion

EMD may facilitate the osteogenic differentiation of BMSCs via activating the Wnt/β-catenin pathway in HG.

Guariguata L, Whiting DR, Hambleton I, Beagley J, Linnenkamp U, Shaw JE (2014) Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res Clin Pract 103:137–149PubMedCrossRef

Cole Joanne B, Florez Jose C (2020) Genetics of diabetes mellitus and diabetes complications. Nat Rev Nephrol 16:377–390PubMedCrossRef

Dreyer H, Grischke J, Tiede C, Eberhard J, Schweitzer A, Toikkanen SE, Glöckner S, Krause G, Stiesch M (2018) Epidemiology and risk factors of peri-implantitis: a systematic review. J Periodont Res 53:657–681CrossRef

Elangovan S, Brogden KA, Dawson DV, Blanchette D, Pagan-Rivera K, Stanford CM, Johnson GK, Recker E, Bowers R, Haynes WG, Avila-Ortiz G (2014) Body fat indices and biomarkers of inflammation: a cross-sectional study with implications for obesity and peri-implant oral health. Int J Oral Maxillofac Implants 29:1429–1434CrossRef

Wang W, Zhang X, Zheng J, Yang J (2010) High glucose stimulates adipogenic and inhibits osteogenic differentiation in MG-63 cells through cAMP/protein kinase A/extracellular signal-regulated kinase pathway. Mol Cell Biochem 338:115–122CrossRef

Miron RJ, Sculean A, Cochran DL, Froum S, Zucchelli G, Nemcovsky C, Donos N, Lyngstadaas SP, Deschner J, Dard M, Stavropoulos A, Zhang Y, Trombelli L, Kasaj A, Shirakata Y, Cortellini P, Tonetti M, Rasperini G, Jepsen S, Bosshardt DD (2016) Twenty years of enamel matrix derivative: the past, the present and the future. J Clin Periodontol 43:668–683PubMedCrossRef

Lyngstadaas SP, Wohlfahrt JC, Brookes SJ, Paine ML, Snead ML, Reseland JE (2009) Enamel matrix proteins; old molecules for new applications. Orthod Craniofac Res 12:243–253PubMedPubMedCentralCrossRef

Liu H, Wei LK, Jian XF, Huang J, Zou H, Zhang SZ, Yuan GH (2018) Isolation, culture and induced differentiation of rabbit mesenchymal stem cells into osteoblasts. Exp Ther Med 15:3715–3724

Luo Y, Zhang Y, Miao G, Zhang Y, Liu Y, Huang Y (2019) Runx1 regulates osteogenic differentiation of BMSCs by inhibiting adipogenesis through Wnt/β-catenin pathway. Arch Oral Biol 97:176–184CrossRef

10.

Roel N, Hans C (2017) Wnt/β-Catenin signaling, disease, and emerging therapeutic modalities. Cell 169:985–999CrossRef

11.

Keila S, Nemcovsky CE, Moses O, Artzi Z, Weinreb M (2004) In vitro effects of enamel matrix proteins on rat bone marrow cells and gingival fibroblasts. J Dent Res 83:134–138PubMedCrossRef

12.

Ikawa T, Akizuki T, Shujaa Addin A, Fukuba S, Stavropoulos A, Izumi Y (2019) Enamel matrix derivative in liquid form as adjunct to natural bovine bone grafting at buccal bone dehiscence defects at implant sites: an experimental study in beagle dogs. Clin Oral Implants Res 30:989–996CrossRef

13.

Shirakata Y, Eliezer M, Nemcovsky CE, Weinreb M, Dard M, Sculean A, Bosshardt DD, Moses O (2014) Periodontal healing after application of enamel matrix derivative in surgical supra/infrabony periodontal defects in rats with streptozotocin-induced diabetes. J Periodontal Res 49:101CrossRef

14.

Grazieli CM, Corrêa, Mirella, Gomes, Campos, Marcelo, Periodontology MJJo (2013) Histometric analysis of the effect of enamel matrix derivative on the healing of periodontal defects in rats with diabetes. J Periodontol 84:1309–1318CrossRef

15.

Takeda K, Mizutani K, Matsuura T, Kido D, Mikami R, Noda M, Buranasin P, Sasaki Y, Izumi Y (2018) Periodontal regenerative effect of enamel matrix derivative in diabetes. PLoS ONE 13:e0207201CrossRef

16.

Qian C, Zhu C, Yu W, Jiang X, Zhang F, Sun J (2016) Bone morphogenetic protein 2 promotes osteogenesis of bone marrow stromal cells in type 2 diabetic rats via the Wnt signaling pathway. Int J Biochem Cell Biol 80:143–153PubMedCrossRef

17.

Park SY, Kim KH, Park CH, Shin SY, Rhyu IC, Lee YM, Seol YJ (2018) Enhanced bone regeneration by diabetic cell-based adenoviral BMP-2 Gene therapy in diabetic animals. Tissue Eng Part A 24:930–942CrossRef

18.

Sun Y, Zhu Y, Liu X, Chai Y, Xu J (2020) Morroniside attenuates high glucose-induced BMSC dysfunction by regulating the Glo1/AGE/RAGE axis. Cell Prolif 53:e12866

19.

Cheng L, Li Y, Xia Q, Meng M, Ye Z, Tang Z, Feng H, Chen X, Chen H, Zeng X, Luo Y, Dong Q (2021) Enamel matrix derivative (EMD) enhances the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Bioengineered 12:7033–7045PubMedPubMedCentralCrossRef

20.

Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop D, Horwitz E (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8:315–317PubMedCrossRef

21.

Shi R, Huang Y, Ma C, Wu C, Tian W (2019) Current advances for bone regeneration based on tissue engineering strategies. Front Med 13:160–188CrossRef

22.

Tencerova M, Rendina-Ruedy E, Neess D, Færgeman N, Figeac F, Ali D, Danielsen M, Haakonsson A, Rosen CJ, Kassem M (2019) Metabolic programming determines the lineage-differentiation fate of murine bone marrow stromal progenitor cells. Bone Res 7:35CrossRef

23.

Zhang B, Liu N, Shi H, Wu H, Gao Y, He H, Gu B, Liu H (2016) High glucose microenvironments inhibit the proliferation and migration of bone mesenchymal stem cells by activating GSK3β. J Bone Miner Metab 34:140–150CrossRef

24.

Quan X, Jingyi F, Xiaolei Z (2021) Semaphorin3B promotes proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells in a high-glucose microenvironment. Stem Cells Int 2021:6637176

25.

Shao J, Liu S, Zheng X, Chen J, Li L, Zhu Z (2021) Berberine promotes peri-implant osteogenesis in diabetic rats by ROS-mediated IRS-1 pathway. BioFactors 47:80–92CrossRef

26.

Wang J, Wang B, Li Y, Wang D, Lingling E, Bai Y and Liu H (2013) High glucose inhibits osteogenic differentiation through the BMP signaling pathway in bone mesenchymal stem cells in mice. EXCLI J 12:584–597

27.

Wyganowska-Swiatkowska M, Urbaniak P, Lipinski D, Szalata M, Kotwicka M (2017) Human gingival fibroblast response to enamel matrix derivative, porcine recombinant 213-kDa amelogenin and 53-kDa tyrosine-rich amelogenin peptide. Hum Cell 30:181–191CrossRef

28.

Guergana T, Brigitte S (2020) The double dealing of cyclin D1. Cell Cycle 19:163–178CrossRef

29.

Zhao Z, Zhao M, Xiao G, Franceschi RT (2005) Gene transfer of the Runx2 transcription factor enhances osteogenic activity of bone marrow stromal cells in vitro and in vivo. Mol Ther 12:247–253CrossRef

30.

Toshihisa K (2005) Regulation of skeletal development by the Runx family of transcription factors. J Cell Biochem 95:445–453CrossRef

31.

Pérez-Campo FM, Santurtún A, García-Ibarbia C, Pascual MA, Valero C, Garcés C, Sañudo C, Zarrabeitia MT, Riancho JA (2016) Osterix and RUNX2 are transcriptional regulators of sclerostin in human bone. Calcif Tissue Int 99:302–309PubMedCrossRef

32.

Rossert J, Terraz C, Dupont S (2000) Regulation of type I collagen genes expression. Nephrol Dial Transplant 15:66–68PubMedCrossRef

33.

Ortuño MJ, Susperregui AR, Artigas N, Rosa JL, Ventura F (2013) Osterix induces Col1a1 gene expression through binding to Sp1 sites in the bone enhancer and proximal promoter regions. Bone 52:548–556CrossRef

34.

Miron RJ, Chandad F, Buser D, Sculean A, Cochran DL, Zhang Y (2016) Effect of enamel matrix derivative liquid on osteoblast and periodontal ligament cell proliferation and differentiation. J Periodontol 87:91–99PubMedCrossRef

35.

McCarthy TL, Centrella M (2010) Novel links among Wnt and TGF-beta signaling and Runx2. Mol Endocrinol 24:587–597PubMedPubMedCentralCrossRef

36.

Behrens J, von Kries JP, Kühl M, Bruhn L, Wedlich D, Grosschedl R, Birchmeier W (1996) Functional interaction of beta-catenin with the transcription factor LEF-1. Nature 382:638–642PubMedCrossRef

37.

Li Z, Zhao H, Chu S, Liu X, Qu X, Li J, Liu D, Li H (2020) miR-124–3p promotes BMSC osteogenesis via suppressing the GSK-3β/β-catenin signaling pathway in diabetic osteoporosis rats. In Vitro Cell Dev Biol Anim 56:723–734CrossRef

38.

Afifi MM, Austin LA, Mackey MA, El-Sayed MA (2014) XAV939: from a small inhibitor to a potent drug bioconjugate when delivered by gold nanoparticles. Bioconjug Chem 25:207–215PubMedPubMedCentralCrossRef

39.

Peng Y, Shi K, Wang L, Lu J, Li H, Pan S, Ma C (2013) Characterization of Osterix protein stability and physiological role in osteoblast differentiation. PLoS ONE 8:e56451CrossRef

Titel: Enamel matrix derivative expedites osteogenic differentiation of BMSCs via Wnt/β-catenin pathway in high glucose microenvironment
verfasst von: MaoHua Meng
Qian Xia
Ying Li
Xin Chen
QinYing Wang
JingQiao Chen
XingXing Xu
Huan Wang
JiaYu Shu
Jing Lu
Lu Cheng
ZhaoYang Ye
Bin Song
Qiang Dong
Publikationsdatum: 27.03.2022
Verlag: Springer Nature Singapore
Erschienen in: Journal of Bone and Mineral Metabolism / Ausgabe 3/2022
Print ISSN: 0914-8779
Elektronische ISSN: 1435-5604
DOI: https://doi.org/10.1007/s00774-022-01318-6

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Enamel matrix derivative expedites osteogenic differentiation of BMSCs via Wnt/β-catenin pathway in high glucose microenvironment