nach oben

Calcified Tissue International

Erschienen in:

09.03.2018 | Original Research

MicroRNA-218 Promotes Osteogenic Differentiation of Mesenchymal Stem Cells and Accelerates Bone Fracture Healing

verfasst von: Liu Shi, Lu Feng, Yang Liu, Ji-qiang Duan, Wei-ping Lin, Jin-fang Zhang, Gang Li

Erschienen in: Calcified Tissue International | Ausgabe 2/2018

Einloggen, um Zugang zu erhalten

Abstract

As a regulator of osteogenesis, microRNA-218 (miR-218) is reported to promote osteogenesis of mesenchymal stem cells (MSCs). However, the in vivo osteogenic effect of miR-218 remains elusive. In this study, miR-218 was confirmed to promote osteogenic differentiation of MSCs by stimulating the alkaline phosphatase activity, calcium nodule formation, and osteogenic marker gene expression. For in vivo study, the miR-218-overexpressing BMSCs were locally administrated into the fracture sites in a femur fracture mouse model. Based on the X-rays, micro-computed tomography, mechanical testing, histology, and immunohistochemistry examinations, miR-218 overexpression improved new bone formation and accelerated fracture healing. These findings suggest that miR-218 may be a promising therapeutic target for bone repair in future clinical applications.

Nur mit Berechtigung zugänglich

Marsell R, Einhorn TA (2011) The biology of fracture healing. Injury 42:551–555CrossRefPubMedPubMedCentral

Phillips AM (2005) Overview of the fracture healing cascade. Injury 36(Suppl 3):S5–S7CrossRefPubMed

Keating JF, Blachut PA, O’Brien PJ, Court-Brown CM (2000) Reamed nailing of Gustilo grade-IIIB tibial fractures. J Bone Joint Surg Br 82:1113–1116CrossRefPubMed

Marsh D (1998) Concepts of fracture union, delayed union, and nonunion. Clin Orthop Relat Res S22–S30

Granero-Molto F, Weis JA, Miga MI, Landis B, Myers TJ, O’Rear L, Longobardi L, Jansen ED, Mortlock DP, Spagnoli A (2009) Regenerative effects of transplanted mesenchymal stem cells in fracture healing. Stem Cells 27:1887–1898CrossRefPubMedPubMedCentral

Lin W, Xu L, Zwingenberger S, Gibon E, Goodman SB, Li G (2017) Mesenchymal stem cells homing to improve bone healing. J Orthop Transl 9:19–27

Ambros V (2004) The functions of animal microRNAs. Nature 431:350–355CrossRefPubMed

Zhang JF, Fu WM, He ML, Xie WD, Lv Q, Wan G, Li G, Wang H, Lu G, Hu X, Jiang S, Li JN, Lin MC, Zhang YO, Kung HF (2011) MiRNA-20a promotes osteogenic differentiation of human mesenchymal stem cells by co-regulating BMP signaling. RNA Biol 8:829–838CrossRefPubMed

Li H, Li T, Fan J, Li T, Fan L, Wang S, Weng X, Han Q, Zhao RC (2015) miR-216a rescues dexamethasone suppression of osteogenesis, promotes osteoblast differentiation and enhances bone formation, by regulating c-Cbl-mediated PI3K/AKT pathway. Cell Death Differ 22:1935–1945CrossRefPubMedPubMedCentral

10.

Trompeter HI, Dreesen J, Hermann E, Iwaniuk KM, Hafner M, Renwick N, Tuschl T, Wernet P (2013) MicroRNAs miR-26a, miR-26b, and miR-29b accelerate osteogenic differentiation of unrestricted somatic stem cells from human cord blood. BMC Genomics 14:111CrossRefPubMedPubMedCentral

11.

Li H, Li T, Wang S, Wei J, Fan J, Li J, Han Q, Liao L, Shao C, Zhao RC (2013) miR-17-5p and miR-106a are involved in the balance between osteogenic and adipogenic differentiation of adipose-derived mesenchymal stem cells. Stem Cell Res 10:313–324CrossRefPubMed

12.

Huang J, Zhao L, Xing L, Chen D (2010) MicroRNA-204 regulates Runx2 protein expression and mesenchymal progenitor cell differentiation. Stem Cells 28:357–364PubMedPubMedCentral

13.

Sun Y, Xu L, Huang S, Hou Y, Liu Y, Chan KM, Pan XH, Li G (2015) mir-21 overexpressing mesenchymal stem cells accelerate fracture healing in a rat closed femur fracture model. BioMed Res Int 2015:412327PubMedPubMedCentral

14.

Sun Y, Xu J, Xu L, Zhang J, Chan K, Pan X, Li G (2017) MiR-503 promotes bone formation in distraction osteogenesis through suppressing Smurf1 expression. Sci Rep 7:409CrossRefPubMedPubMedCentral

15.

Tu M, Tang J, He H, Cheng P, Chen C (2017) MiR-142-5p promotes bone repair by maintaining osteoblast activity. J Bone Miner Metab 35:255–264CrossRefPubMed

16.

Lee WY, Li N, Lin S, Wang B, Lan HY, Li G (2016) miRNA-29b improves bone healing in mouse fracture model. Mol Cell Endocrinol 430:97–107CrossRefPubMed

17.

Amin ND, Bai G, Klug JR, Bonanomi D, Pankratz MT, Gifford WD, Hinckley CA, Sternfeld MJ, Driscoll SP, Dominguez B, Lee KF, Jin X, Pfaff SL (2015) Loss of motoneuron-specific microRNA-218 causes systemic neuromuscular failure, vol 350. Science, New York, pp 1525–1529

18.

Hassan MQ, Maeda Y, Taipaleenmaki H, Zhang W, Jafferji M, Gordon JA, Li Z, Croce CM, van Wijnen AJ, Stein JL, Stein GS, Lian JB (2012) miR-218 directs a Wnt signaling circuit to promote differentiation of osteoblasts and osteomimicry of metastatic cancer cells. J Biol Chem 287:42084–42092CrossRefPubMedPubMedCentral

19.

Zhang WB, Zhong WJ, Wang L (2014) A signal-amplification circuit between miR-218 and Wnt/beta-catenin signal promotes human adipose tissue-derived stem cells osteogenic differentiation. Bone 58:59–66CrossRefPubMed

20.

Zhang Y, Xie RL, Croce CM, Stein JL, Lian JB, van Wijnen AJ, Stein GS (2011) A program of microRNAs controls osteogenic lineage progression by targeting transcription factor Runx2. Proc Natl Acad Sci USA 108:9863–9868CrossRefPubMed

21.

Xu L, Meng F, Ni M, Lee Y, Li G (2013) N-cadherin regulates osteogenesis and migration of bone marrow-derived mesenchymal stem cells. Mol Biol Rep 40:2533–2539CrossRefPubMed

22.

Huang S, Xu L, Sun Y, Wu T, Wang K, Li G (2015) An improved protocol for isolation and culture of mesenchymal stem cells from mouse bone marrow. J. Orthop. Transl. 3:26–33

23.

Liang WC, Wang Y, Xiao LJ, Wang YB, Fu WM, Wang WM, Jiang HQ, Qi W, Wan DC, Zhang JF, Waye MM (2014) Identification of miRNAs that specifically target tumor suppressive KLF6-FL rather than oncogenic KLF6-SV1 isoform. RNA Biol. 11:845–854CrossRefPubMedPubMedCentral

24.

Guo J, Zhang JF, Wang WM, Cheung FW, Lu YF, Ng CF, Kung HF, Liu WK (2014) MicroRNA-218 inhibits melanogenesis by directly suppressing microphthalmia-associated transcription factor expression. RNA Biol 11:732–741CrossRefPubMedPubMedCentral

25.

Xu D, Xu L, Zhou C, Lee WY, Wu T, Cui L, Li G (2014) Salvianolic acid B promotes osteogenesis of human mesenchymal stem cells through activating ERK signaling pathway. Int J biochem Cell Biol 51:1–9CrossRefPubMed

26.

Rui YF, Lui PP, Wong YM, Tan Q, Chan KM (2013) Altered fate of tendon-derived stem cells isolated from a failed tendon-healing animal model of tendinopathy. Stem Cells Dev 22:1076–1085CrossRefPubMed

27.

Huang S, Xu L, Sun Y, Zhang Y, Li G (2015) The fate of systemically administrated allogeneic mesenchymal stem cells in mouse femoral fracture healing. Stem Cell Res Ther 6:206CrossRefPubMedPubMedCentral

28.

He YX, Zhang G, Pan XH, Liu Z, Zheng LZ, Chan CW, Lee KM, Cao YP, Li G, Wei L, Hung LK, Leung KS, Qin L (2011) Impaired bone healing pattern in mice with ovariectomy-induced osteoporosis: a drill-hole defect model. Bone 48:1388–1400CrossRefPubMed

29.

Gomez-Barrena E, Rosset P, Lozano D, Stanovici J, Ermthaller C, Gerbhard F (2015) Bone fracture healing: cell therapy in delayed unions and nonunions. Bone 70:93–101CrossRefPubMed

30.

Waki T, Lee SY, Niikura T, Iwakura T, Dogaki Y, Okumachi E, Oe K, Kuroda R, Kurosaka M (2016) Profiling microRNA expression during fracture healing. BMC Musculoskelet Disord 17:83CrossRefPubMedPubMedCentral

31.

Gay I, Cavender A, Peto D, Sun Z, Speer A, Cao H, Amendt BA (2014) Differentiation of human dental stem cells reveals a role for microRNA-218. J Periodontal Res 49:110–120CrossRefPubMed

32.

Orimo H (2010) The mechanism of mineralization and the role of alkaline phosphatase in health and disease. J Nippon Med Sch 77:4–12CrossRefPubMed

33.

Gordon JA, Tye CE, Sampaio AV, Underhill TM, Hunter GK, Goldberg HA (2007) Bone sialoprotein expression enhances osteoblast differentiation and matrix mineralization in vitro. Bone 41:462–473CrossRefPubMed

34.

Orimo H, Shimada T (2008) The role of tissue-nonspecific alkaline phosphatase in the phosphate-induced activation of alkaline phosphatase and mineralization in SaOS-2 human osteoblast-like cells. Mol Cell Biochem 315:51–60CrossRefPubMed

35.

Nakashima K, Zhou X, Kunkel G, Zhang Z, Deng JM, Behringer RR, de Crombrugghe B (2002) The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell 108:17–29CrossRefPubMed

36.

Tu Q, Valverde P, Chen J (2006) Osterix enhances proliferation and osteogenic potential of bone marrow stromal cells. Biochem Biophys Res Commun 341:1257–1265CrossRefPubMedPubMedCentral

37.

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 12:247–253CrossRefPubMed

38.

Cao Y, Zhou Z, de Crombrugghe B, Nakashima K, Guan H, Duan X, Jia SF, Kleinerman ES (2005) Osterix, a transcription factor for osteoblast differentiation, mediates antitumor activity in murine osteosarcoma. Cancer Res 65:1124–1128CrossRefPubMed

39.

Sowa AK, Kaiser FJ, Eckhold J, Kessler T, Aherrahrou R, Wrobel S, Kaczmarek PM, Doehring L, Schunkert H, Erdmann J, Aherrahrou Z (2013) Functional interaction of osteogenic transcription factors Runx2 and Vdr in transcriptional regulation of Opn during soft tissue calcification. Am J Pathol 183:60–68CrossRefPubMed

Titel: MicroRNA-218 Promotes Osteogenic Differentiation of Mesenchymal Stem Cells and Accelerates Bone Fracture Healing
verfasst von: Liu Shi
Lu Feng
Yang Liu
Ji-qiang Duan
Wei-ping Lin
Jin-fang Zhang
Gang Li
Publikationsdatum: 09.03.2018
Verlag: Springer US
Erschienen in: Calcified Tissue International / Ausgabe 2/2018
Print ISSN: 0171-967X
Elektronische ISSN: 1432-0827
DOI: https://doi.org/10.1007/s00223-018-0410-8

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

25.04.2024 Allergien und Intoleranzreaktionen Nachrichten

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 2/2018

Irradiation-Induced Compositional Effects on Human Bone After Extracorporeal Therapy for Bone Sarcoma

A Novel microCT Method for Bone and Marrow Adipose Tissue Alignment Identifies Key Differences Between Mandible and Tibia in Rats

Selective Serotonin Reuptake Inhibitors (SSRIs) and Markers of Bone Turnover in Men

Alkaline Phosphatases in the Complex Chronic Kidney Disease-Mineral and Bone Disorders

Marrow Adipose Tissue in Older Men: Association with Visceral and Subcutaneous Fat, Bone Volume, Metabolism, and Inflammation