Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
International Journal of Molecular Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1107-3756 Online ISSN: 1791-244X
Journal Cover
July-2016 Volume 38 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
July-2016 Volume 38 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

Zoledronic acid suppresses transforming growth factor-β-induced fibrogenesis by human gingival fibroblasts

  • Authors:
    • Yuko Komatsu
    • Miho Ibi
    • Naoyuki Chosa
    • Seiko Kyakumoto
    • Masaharu Kamo
    • Toshiyuki Shibata
    • Yoshiki Sugiyama
    • Akira Ishisaki
  • View Affiliations / Copyright

    Affiliations: Division of Cellular Biosignal Sciences, Department of Biochemistry, Iwate Medical University, Iwate 028‑3694, Japan, Department of Oral and Maxillofacial Surgery, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan, Division of Oral and Maxillofacial Surgery, Department of Reconstructive Oral and Maxillofacial Surgery, Iwate Medical University, Iwate 020-8505, Japan
    Copyright: © Komatsu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 139-147
    |
    Published online on: May 10, 2016
       https://doi.org/10.3892/ijmm.2016.2582
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Bisphosphonates (BPs) are analogues of pyrophosphate that are known to prevent bone resorption by inhibiting osteoclast activity. Nitrogen-containing BPs, such as zoledronic acid (ZA), are widely used in the treatment of osteoporosis and bone metastasis. However, despite having benefits, ZA has been reported to induce BP-related osteonecrosis of the jaw (BRONJ) in cancer patients. The molecular pathological mechanisms responsible for the development of BRONJ, including necrotic bone exposure after tooth extraction, remain to be elucidated. In this study, we examined the effects of ZA on the transforming growth factor-β (TGF‑β)-induced myofibroblast (MF) differentiation of human gingival fibroblasts (hGFs) and the migratory activity of hGFs, which are important for wound closure by fibrous tissue formation. The ZA maximum concentration in serum (Cmax) was found to be approximately 1.47 µM, which clinically, is found after the intravenous administration of 4 mg ZA, and ZA at this dose is considered appropriate for the treatment of cancer bone metastasis or bone diseases, such as Erdheim-Chester disease. At Cmax, ZA significantly suppressed i) the TGF‑β-induced promotion of cell viability, ii) the TGF‑β-induced expression of MF markers such as α-smooth muscle actin (α-SMA) and type I collagen, iii) the TGF‑β-induced migratory activity of hGFs and iv) the expression level of TGF‑β type I receptor on the surfaces of hGFs, as well as the TGF‑β-induced phosphorylation of Smad2/3. Thus, ZA suppresses TGF‑β-induced fibrous tissue formation by hGFs, possibly through the inhibition of Smad‑dependent signal transduction. Our findings partly elucidate the molecular mechanisms underlying BRONJ and may prove to be beneficial to the identification of drug targets for the treatment of this symptom at the molecular level.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Gong L, Altman RB and Klein TE: Bisphosphonates pathway. Pharmacogenet Genomics. 21:50–53. 2011. View Article : Google Scholar :

2 

Boonyapakorn T, Schirmer I, Reichart PA, Sturm I and Massenkeil G: Bisphosphonate-induced osteonecrosis of the jaws: prospective study of 80 patients with multiple myeloma and other malignancies. Oral Oncol. 44:857–869. 2008. View Article : Google Scholar : PubMed/NCBI

3 

Fliefel R, Tröltzsch M, Kühnisch J, Ehrenfeld M and Otto S: Treatment strategies and outcomes of bisphosphonate-related osteonecrosis of the jaw (BRONJ) with characterization of patients: a systematic review. Int J Oral Maxillofac Surg. 44:568–585. 2015. View Article : Google Scholar : PubMed/NCBI

4 

Manaka K, Makita N and Iiri T: Erdheim-Chester disease and pituitary involvement: a unique case and the literature. Endocr J. 61:185–194. 2014. View Article : Google Scholar

5 

Rogers MJ, Crockett JC, Coxon FP and Mönkkönen J: Biochemical and molecular mechanisms of action of bisphosphonates. Bone. 49:34–41. 2011. View Article : Google Scholar

6 

Vahtsevanos K, Kyrgidis A, Verrou E, Katodritou E, Triaridis S, Andreadis CG, Boukovinas I, Koloutsos GE, Teleioudis Z, Kitikidou K, et al: Longitudinal cohort study of risk factors in cancer patients of bisphosphonate-related osteonecrosis of the jaw. J Clin Oncol. 27:5356–5362. 2009. View Article : Google Scholar : PubMed/NCBI

7 

Marx RE, Sawatari Y, Fortin M and Broumand V: Bisphosphonate-induced exposed bone (osteonecrosis/osteopetrosis) of the jaws: risk factors, recognition, prevention, and treatment. J Oral Maxillofac Surg. 63:1567–1575. 2005. View Article : Google Scholar : PubMed/NCBI

8 

Ruggiero SL, Dodson TB, Assael LA, Landesberg R, Marx RE and Mehrotra B; American Association of Oral and Maxillofacial Surgeons: American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonate-related osteonecrosis of the jaws. J Oral Maxillofac Surg. 67(Suppl 5): 2–12. 2009.PubMed/NCBI

9 

Hansen T, Kunkel M, Weber A and James Kirkpatrick C: Osteonecrosis of the jaws in patients treated with bisphosphonates-histomorpholoic analysis in comparison with infected osteoradionecrosis. J Oral Pathol Med. 35:155–160. 2006. View Article : Google Scholar : PubMed/NCBI

10 

Hoefert S, Wierich W, Eufinger H and Krempien B: BP-associated vascular necrosis (AN) of the jaws: histological findings. Bone. 38(suppl 1): 762006. View Article : Google Scholar

11 

De Ceulaer J, Tacconelli E and Vandecasteele SJ: Actinomyces osteomyelitis in bisphosphonate-related osteonecrosis of the jaw (BRONJ): the missing link? Eur J Clin Microbiol Infect Dis. 33:1873–1880. 2014. View Article : Google Scholar : PubMed/NCBI

12 

Kobayashi Y, Hiraga T, Ueda A, Wang L, Matsumoto-Nakano M, Hata K, Yatani H and Yoneda T: Zoledronic acid delays wound healing of the tooth extraction socket, inhibits oral epithelial cell migration, and promotes proliferation and adhesion to hydroxyapatite of oral bacteria, without causing osteonecrosis of the jaw, in mice. J Bone Miner Metab. 28:165–175. 2010. View Article : Google Scholar

13 

Berti-Couto SA, Vasconcelos AC, Iglesias JE, Figueiredo MA, Salum FG and Cherubini K: Diabetes mellitus and corticotherapy as risk factors for alendronate-related osteonecrosis of the jaws: a study in Wistar rats. Head Neck. 36:84–93. 2014. View Article : Google Scholar

14 

Molcho S, Peer A, Berg T, Futerman B and Khamaisi M: Diabetes microvascular disease and the risk for bisphosphonate-related osteonecrosis of the jaw: A single center study. J Clin Endocrinol Metab. 98:E1807–E1812. 2013. View Article : Google Scholar : PubMed/NCBI

15 

Nisi M, La Ferla F, Karapetsa D, Gennai S, Miccoli M, Baggiani A, Graziani F and Gabriele M: Risk factors influencing BRONJ staging in patients receiving intravenous bisphosphonates: a multivariate analysis. Int J Oral Maxillofac Surg. 44:586–591. 2015. View Article : Google Scholar : PubMed/NCBI

16 

Valluru M, Staton CA, Reed MWR and Brown NJ: Transforming growth factor-β and endoglin signaling orchestrate wound healing. Front Physiol. 2:892011. View Article : Google Scholar

17 

Tipton DA and Dabbous MK: Autocrine transforming growth factor β stimulation of extracellular matrix production by fibroblasts from fibrotic human gingiva. J Periodontol. 69:609–619. 1998. View Article : Google Scholar : PubMed/NCBI

18 

Cotrim P, Martelli-Junior H, Graner E, Sauk JJ and Coletta RD: Cyclosporin A induces proliferation in human gingival fibroblasts via induction of transforming growth factor-beta1. J Periodontol. 74:1625–1633. 2003. View Article : Google Scholar : PubMed/NCBI

19 

Wu MY and Hill CS: TGF-β superfamily signaling in embryonic development and homeostasis. Dev Cell. 16:329–343. 2009. View Article : Google Scholar : PubMed/NCBI

20 

Goumans MJ, Liu Z and ten Dijke P: TGF-β signaling in vascular biology and dysfunction. Cell Res. 19:116–127. 2009. View Article : Google Scholar

21 

Heldin CH, Landström M and Moustakas A: Mechanism of TGF-β signaling to growth arrest, apoptosis, and epithelial-mesenchymal transition. Curr Opin Cell Biol. 21:166–176. 2009. View Article : Google Scholar : PubMed/NCBI

22 

Liu T and Feng XH: Regulation of TGF-β signalling by protein phosphatases. Biochem J. 430:191–198. 2010. View Article : Google Scholar : PubMed/NCBI

23 

Meulmeester E and Ten Dijke P: The dynamic roles of TGF-β in cancer. J Pathol. 223:205–218. 2011. View Article : Google Scholar

24 

Song B, Estrada KD and Lyons KM: Smad signaling in skeletal development and regeneration. Cytokine Growth Factor Rev. 20:379–388. 2009. View Article : Google Scholar : PubMed/NCBI

25 

Sandbo N and Dulin N: Actin cytoskeleton in myofibroblast differentiation: ultrastructure defining form and driving function. Transl Res. 158:181–196. 2011. View Article : Google Scholar : PubMed/NCBI

26 

Kimura H, Okubo N, Chosa N, Kyakumoto S, Kamo M, Miura H and Ishisaki A: EGF positively regulates the proliferation and migration, and negatively regulates the myofibroblast differentiation of periodontal ligament-derived endothelial progenitor cells through MEK/ERK- and JNK-dependent signals. Cell Physiol Biochem. 32:899–914. 2013. View Article : Google Scholar : PubMed/NCBI

27 

Sobral LM, Montan PF, Zecchin KG, Martelli-Junior H, Vargas PA, Graner E and Coletta RD: Smad7 blocks transforming growth factor-β1-induced gingival fibroblast-myofibroblast transition via inhibitory regulation of Smad2 and connective tissue growth factor. J Periodontol. 82:642–651. 2011. View Article : Google Scholar

28 

Motizuki M, Isogaya K, Miyake K, Ikushima H, Kubota T, Miyazono K, Saitoh M and Miyazawa K: Oligodendrocyte transcription factor 1 (Olig1) is a Smad cofactor involved in cell motility induced by transforming growth factor-β. J Biol Chem. 288:18911–18922. 2013. View Article : Google Scholar : PubMed/NCBI

29 

Nakano N, Maeyama K, Sakata N, Itoh F, Akatsu R, Nakata M, Katsu Y, Ikeno S, Togawa Y, Vo Nguyen TT, et al: C18 ORF1, a novel negative regulator of transforming growth factor-β signaling. J Biol Chem. 289:12680–12692. 2014. View Article : Google Scholar : PubMed/NCBI

30 

Xiao Y-Q, Liu K, Shen J-F, Xu G-T and Ye W: SB-431542 inhibition of scar formation after filtration surgery and its potential mechanism. Invest Ophthalmol Vis Sci. 50:1698–1706. 2009. View Article : Google Scholar

31 

Bakin AV, Rinehart C, Tomlinson AK and Arteaga CL: p38 mitogen-activated protein kinase is required for TGFbeta-mediated fibroblastic transdifferentiation and cell migration. J Cell Sci. 115:3193–3206. 2002.PubMed/NCBI

32 

Sarrazy V, Billet F, Micallef L, Coulomb B and Desmoulière A: Mechanisms of pathological scarring: role of myofibroblasts and current developments. Wound Repair Regen. 19(Suppl 1): s10–s15. 2011. View Article : Google Scholar : PubMed/NCBI

33 

Van De Water L, Varney S and Tomasek JJ: Mechanoregulation of the myofibroblast in wound contraction, scarring, and fibrosis: Opportunities for new therapeutic intervention. Adv Wound Care (New Rochelle). 2:122–141. 2013. View Article : Google Scholar

34 

Hinz B: Formation and function of the myofibroblast during tissue repair. J Invest Dermatol. 127:526–537. 2007. View Article : Google Scholar : PubMed/NCBI

35 

Yoshinami T, Yagi T, Sakai D, Sugimoto N and Imamura F: A case of acquired Fanconi syndrome induced by zoledronic acid. Intern Med. 50:1075–1079. 2011. View Article : Google Scholar : PubMed/NCBI

36 

Kurishima K, Ohara G, Kagohashi K, Takayashiki N, Tamura T, Shiozawa T, Miyazaki K, Kawaguchi M, Satoh H and Hizawa N: Ossification and increased bone mineral density with zoledronic acid in a patient with lung adenocarcinoma: a case report. Exp Ther Med. 8:1267–1270. 2014.PubMed/NCBI

37 

DeMaio L, Buckley ST, Krishnaveni MS, Flodby P, Dubourd M, Banfalvi A, Xing Y, Ehrhardt C, Minoo P, Zhou B, et al: Ligand-independent transforming growth factor-β type I receptor signalling mediates type I collagen-induced epithelial-mesenchymal transition. J Pathol. 226:633–644. 2012. View Article : Google Scholar

38 

Xu X, Wan X, Geng J, Li F, Wang C and Dai H: Kinase inhibitors fail to induce mesenchymal-epithelial transition in fibroblasts from fibrotic lung tissue. Int J Mol Med. 32:430–438. 2013.PubMed/NCBI

39 

Sawada S, Chosa N, Ishisaki A and Naruishi K: Enhancement of gingival inflammation induced by synergism of IL-1β and IL-6. Biomed Res. 34:31–40. 2013. View Article : Google Scholar : PubMed/NCBI

40 

Wang X, Chu J, Wen CJ, Fu SB, Qian YL, Wo Y, Wang C and Wang DR: Functional characterization of TRAP1-like protein involved in modulating fibrotic processes mediated by TGF-β/Smad signaling in hypertrophic scar fibroblasts. Exp Cell Res. 332:202–211. 2015. View Article : Google Scholar : PubMed/NCBI

41 

Lu Q: Transforming growth factor-beta1 protects against pulmonary artery endothelial cell apoptosis via ALK5. Am J Physiol Lung Cell Mol Physiol. 295:L123–L133. 2008. View Article : Google Scholar : PubMed/NCBI

42 

Pan B, To LB, Farrugia AN, Findlay DM, Green J, Gronthos S, Evdokiou A, Lynch K, Atkins GJ and Zannettino AC: The nitrogen-containing bisphosphonate, zoledronic acid, increases mineralisation of human bone-derived cells in vitro. Bone. 34:112–123. 2004. View Article : Google Scholar : PubMed/NCBI

43 

Koch FP, Merkel C, Al-Nawas B, Smeets R, Ziebart T, Walter C and Wagner W: Zoledronate, ibandronate and clodronate enhance osteoblast differentiation in a dose dependent manner - a quantitative in vitro gene expression analysis of Dlx5, Runx2, OCN, MSX1 and MSX2. J Craniomaxillofac Surg. 39:562–569. 2011. View Article : Google Scholar

44 

Chen YJ, Chao KS, Yang YC, Hsu ML, Lin CP and Chen YY: Zoledronic acid, an aminobisphosphonate, modulates differentiation and maturation of human dendritic cells. Immunopharmacol Immunotoxicol. 31:499–508. 2009. View Article : Google Scholar : PubMed/NCBI

45 

Pabst AM, Ziebart T, Koch FP, Taylor KY, Al-Nawas B and Walter C: The influence of bisphosphonates on viability, migration, and apoptosis of human oral keratinocytes - in vitro study. Clin Oral Investig. 16:87–93. 2012. View Article : Google Scholar

46 

Tarnawski AS: Cellular and molecular mechanisms of gastrointestinal ulcer healing. Dig Dis Sci. 50(Suppl 1): S24–S33. 2005. View Article : Google Scholar : PubMed/NCBI

47 

Ozdamar B, Bose R, Barrios-Rodiles M, Wang HR, Zhang Y and Wrana JL: Regulation of the polarity protein Par6 by TGFbeta receptors controls epithelial cell plasticity. Science. 307:1603–1609. 2005. View Article : Google Scholar : PubMed/NCBI

48 

Tojkander S, Gateva G and Lappalainen P: Actin stress fibers - assembly, dynamics and biological roles. J Cell Sci. 125:1855–1864. 2012. View Article : Google Scholar : PubMed/NCBI

49 

Saito T, Izumi K, Shiomi A, Uenoyama A, Ohnuki H, Kato H, Terada M, Nozawa-Inoue K, Kawano Y, Takagi R and Maeda T: Zoledronic acid impairs re-epithelialization through down-regulation of integrin αvβ6 and transforming growth factor beta signalling in a three-dimensional in vitro wound healing model. Int J Oral Maxillofac Surg. 43:373–380. 2014. View Article : Google Scholar

50 

Okamoto S, Jiang Y, Kawamura K, Shingyoji M, Tada Y, Sekine I, Takiguchi Y, Tatsumi K, Kobayashi H, Shimada H, et al: Zoledronic acid induces apoptosis and S-phase arrest in mesothelioma through inhibiting Rab family proteins and topoisomerase II actions. Cell Death Dis. 5:e15172014. View Article : Google Scholar : PubMed/NCBI

51 

Aloisi AL and Bucci C: Rab GTPases-cargo direct interactions: fine modulators of intracellular trafficking. Histol Histopathol. 28:839–849. 2013.PubMed/NCBI

52 

Hu H, Milstein M, Bliss JM, Thai M, Malhotra G, Huynh LC and Colicelli J: Integration of transforming growth factor beta and RAS signaling silences a RAB5 guanine nucleotide exchange factor and enhances growth factor-directed cell migration. Mol Cell Biol. 28:1573–1583. 2008. View Article : Google Scholar

53 

Kardassis D, Murphy C, Fotsis T, Moustakas A and Stournaras C: Control of transforming growth factor β signal transduction by small GTPases. FEBS J. 276:2947–2965. 2009. View Article : Google Scholar : PubMed/NCBI

54 

Short M, Nemenoff RA, Zawada WM, Stenmark KR and Das M: Hypoxia induces differentiation of pulmonary artery adventitial fibroblasts into myofibroblasts. Am J Physiol Cell Physiol. 286:C416–C425. 2004. View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Komatsu Y, Ibi M, Chosa N, Kyakumoto S, Kamo M, Shibata T, Sugiyama Y and Ishisaki A: Zoledronic acid suppresses transforming growth factor-β-induced fibrogenesis by human gingival fibroblasts. Int J Mol Med 38: 139-147, 2016.
APA
Komatsu, Y., Ibi, M., Chosa, N., Kyakumoto, S., Kamo, M., Shibata, T. ... Ishisaki, A. (2016). Zoledronic acid suppresses transforming growth factor-β-induced fibrogenesis by human gingival fibroblasts. International Journal of Molecular Medicine, 38, 139-147. https://doi.org/10.3892/ijmm.2016.2582
MLA
Komatsu, Y., Ibi, M., Chosa, N., Kyakumoto, S., Kamo, M., Shibata, T., Sugiyama, Y., Ishisaki, A."Zoledronic acid suppresses transforming growth factor-β-induced fibrogenesis by human gingival fibroblasts". International Journal of Molecular Medicine 38.1 (2016): 139-147.
Chicago
Komatsu, Y., Ibi, M., Chosa, N., Kyakumoto, S., Kamo, M., Shibata, T., Sugiyama, Y., Ishisaki, A."Zoledronic acid suppresses transforming growth factor-β-induced fibrogenesis by human gingival fibroblasts". International Journal of Molecular Medicine 38, no. 1 (2016): 139-147. https://doi.org/10.3892/ijmm.2016.2582
Copy and paste a formatted citation
x
Spandidos Publications style
Komatsu Y, Ibi M, Chosa N, Kyakumoto S, Kamo M, Shibata T, Sugiyama Y and Ishisaki A: Zoledronic acid suppresses transforming growth factor-β-induced fibrogenesis by human gingival fibroblasts. Int J Mol Med 38: 139-147, 2016.
APA
Komatsu, Y., Ibi, M., Chosa, N., Kyakumoto, S., Kamo, M., Shibata, T. ... Ishisaki, A. (2016). Zoledronic acid suppresses transforming growth factor-β-induced fibrogenesis by human gingival fibroblasts. International Journal of Molecular Medicine, 38, 139-147. https://doi.org/10.3892/ijmm.2016.2582
MLA
Komatsu, Y., Ibi, M., Chosa, N., Kyakumoto, S., Kamo, M., Shibata, T., Sugiyama, Y., Ishisaki, A."Zoledronic acid suppresses transforming growth factor-β-induced fibrogenesis by human gingival fibroblasts". International Journal of Molecular Medicine 38.1 (2016): 139-147.
Chicago
Komatsu, Y., Ibi, M., Chosa, N., Kyakumoto, S., Kamo, M., Shibata, T., Sugiyama, Y., Ishisaki, A."Zoledronic acid suppresses transforming growth factor-β-induced fibrogenesis by human gingival fibroblasts". International Journal of Molecular Medicine 38, no. 1 (2016): 139-147. https://doi.org/10.3892/ijmm.2016.2582
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team