nach oben

Erschienen in:

20.10.2016 | Original Article

Local delivery of recombinant human FGF7 enhances bone formation in rat mandible defects

verfasst von: Sher Bahadur Poudel, Govinda Bhattarai, Jae-Hwan Kim, Sung-Ho Kook, Young-Kwon Seo, Young-Mi Jeon, Jeong-Chae Lee

Erschienen in: Journal of Bone and Mineral Metabolism | Ausgabe 5/2017

Einloggen, um Zugang zu erhalten

Abstract

Fibroblast growth factor 7 (FGF7) plays an important role in regulating the proliferation, migration, and differentiation of cells. However, the role of FGF7 in bone formation is not yet fully understood. We examined the effect of FGF7 on bone formation using a rat model of mandible defects. Rats underwent mandible defect surgery and then either scaffold treatment alone (control group) or FGF7-impregnated scaffold treatment (FGF7 group). Micro-CT and histological analyses revealed that the FGF7 group exhibited greater bone formation than did the control group 10 weeks after surgery. With the exception of total porosity (%), all bone parameters had higher values in the FGF7 group than in the control group at each follow-up after surgery. The FGF7 group showed greater expression of osteogenic markers, such as runt-related transcription factor 2, osterix, osteocalcin, bone morphogenetic protein 2, osteopontin, and type I collagen in newly formed bone than did the control group. The delivery of FGF7 also increased the messenger RNA expression of stromal-cell-derived factor 1 (SDF-1) and CXCR4 in newly formed bone in the FGF7 group compared with the control group. Further, addition of exogenous FGF7 induced migration of rat bone marrow stromal cells and increased the expression of SDF-1 and CXCR4 in the cells. Furthermore, the addition of FGF7 augmented mineralization in the cells with increased expression of osteogenic markers, and this augmentation was significantly suppressed by an inhibitor specific for c-Jun N-terminal kinase (SP600125) or extracellular-signal-regulated kinase (PD98059). Collectively, these results suggest that local delivery of FGF7 increases bone formation in a mandible defect with enhanced osteogenesis and chemoattraction.

Belov AA, Mohammadi M (2013) Molecular mechanisms of fibroblast growth factor signaling in physiology and pathology. Cold Spring Harb Perspect Biol 5:a015958

Turner N, Grose R (2010) Fibroblast growth factor signalling: from development to cancer. Nat Rev Cancer 10:116–129CrossRefPubMed

Du X, Xie Y, Xian CJ, Chen L (2012) Role of FGFs/FGFRs in skeletal development and bone regeneration. J Cell Physiol 227:3731–3743CrossRefPubMed

Su N, Jin M, Chen L (2014) Role of FGF/FGFR signaling in skeletal development and homeostasis: learning from mouse models. Bone Res 2:14003CrossRefPubMedPubMedCentral

Ornitz DM, Marie PJ (2015) Fibroblast growth factor signaling in skeletal development and disease. Genes Dev 29:1463–1486CrossRefPubMedPubMedCentral

Ornitz DM, Itoh N (2015) The fibroblast growth factor signaling pathway. Wiley Interdiscip Rev Dev Biol 4:215–266CrossRefPubMedPubMedCentral

Beenken A, Mohammadi M (2009) The FGF family: biology, pathophysiology and therapy. Nat Rev Drug Discov 8:235–253CrossRefPubMedPubMedCentral

Sleeman M, Fraser J, McDonald M, Yuan S, White D, Grandison P, Kumble K, Watson JD, Murison JG (2001) Identification of a new fibroblast growth factor receptor, FGFR5. Gene 271:171–182CrossRefPubMed

Yun YR, Won JE, Jeon E, Lee S, Kang W, Jo H, Jang JH, Shin US, Kim HW (2010) Fibroblast growth factors: biology, function, and application for tissue regeneration. J Tissue Eng 2010:218142CrossRefPubMedPubMedCentral

10.

Finch PW, Rubin JS, Miki T, Ron D, Aaronson SA (1989) Human KGF is FGF-related with properties of a paracrine effector of epithelial cell growth. Science 245:752–755CrossRefPubMed

11.

Tsuboi R, Sato C, Kurita Y, Ron D, Rubin JS, Ogawa H (1993) Keratinocyte growth factor (FGF-7) stimulates migration and plasminogen activator activity of normal human keratinocytes. J Invest Dermatol 101:49–53CrossRefPubMed

12.

Peng C, Chen B, Kao HK, Murphy G, Orgill DP, Guo L (2011) Lack of FGF-7 further delays cutaneous wound healing in diabetic mice. Plast Reconstr Surg 128:673e–684eCrossRefPubMed

13.

Pastar I, Stojadinovic O, Yin NC, Ramirez H, Nusbaum AG, Sawaya A, Patel SB, Khalid L, Isseroff RR, Tomic-Canic M (2014) Epithelialization in wound healing: a comprehensive review. Adv Wound Care (New Rochelle) 3:445–464CrossRef

14.

Bruinsma M, van Soest PL, Leenen PJ, Lowenberg B, Cornelissen JJ, Braakman E (2009) Keratinocyte growth factor improves allogeneic bone marrow engraftment through a CD4⁺Foxp3⁺ regulatory T cell-dependent mechanism. J Immunol 82:7364–7369CrossRef

15.

Feng ZG, Pang SF, Guo DJ, Yang YT, Liu B, Wang JW, Zheng KQ, Lin Y (2014) Recombinant keratinocyte growth factor 1 in tobacco potentially promotes wound healing in diabetic rats. Biomed Res Int 2014:579632PubMedPubMedCentral

16.

Jeon YM, Kook SH, Rho SJ, Lim SS, Choi KC, Kim HS, Kim JG, Lee JC (2013) Fibroblast growth factor-7 facilitates osteogenic differentiation of embryonic stem cells through the activation of ERK/Runx2 signaling. Mol Cell Biochem 382:37–45CrossRefPubMed

17.

Kook SH, Jeon YM, Park SS, Lee JC (2014) Periodontal fibroblasts modulate proliferation and osteogenic differentiation of embryonic stem cells through production of fibroblast growth factors. J Periodontol 85:645–654CrossRefPubMed

18.

Yen TT, Thao DT, Thuoc TL (2014) An overview on keratinocyte growth factor: from the molecular properties to clinical applications. Protein Pept Lett 21:306–317CrossRefPubMed

19.

Lim SS, Kook SH, Bhattarai G, Cho ES, Seo YK, Lee JC (2015) Local delivery of COMP-angiopoietin 1 accelerates new bone formation in rat calvarial defects. J Biomed Mater Res A 103:2942–2951CrossRefPubMed

20.

Dimitriou R, Jones E, McGonagle D, Giannoudis PV (2011) Bone regeneration: current concepts and future directions. BMC Med 9:66CrossRefPubMedPubMedCentral

21.

Marsh D (1998) Concepts of fracture union, delayed union, and nonunion. Clin Orthop Relat Res 355:S22–S30CrossRef

22.

Poser L, Matthys R, Schawalder P, Pearce S, Alini M, Zeiter S (2014) A standardized critical size defect model in normal and osteoporotic rats to evaluate bone tissue engineered constructs. Biomed Res Int 2014:348635CrossRefPubMedPubMedCentral

23.

Tzioupis C, Giannoudis PV (2007) Prevalence of long-bone non-unions. Injury 38:S3–S9CrossRefPubMed

24.

Oryan A, Alidadi S, Moshiri A, Maffulli N (2014) Bone regenerative medicine: classic options, novel strategies, and future directions. J Orthop Surg Res 9:18CrossRefPubMedPubMedCentral

25.

Roberts TT, Rosenbaum AJ (2012) Grafts Bone, bone substitutes and orthobiologics: the bridge between basic science and clinical advancements in fracture healing. Organogenesis 8:114–124CrossRefPubMedPubMedCentral

26.

Jimi E, Hirata S, Osawa K, Terashita M, Kitamura C, Fukushima H (2012) The current and future therapies of bone regeneration to repair bone defects. Int J Dent 2012:148261CrossRefPubMedPubMedCentral

27.

Hegde C, Shetty V, Wasnik S, Ahammed I, Shetty V (2013) Use of bone graft substitute in the treatment for distal radius fractures in elderly. Eur J Orthop Surg Traumatol 23:651–656CrossRefPubMed

28.

Younger EM, Chapman MW (1989) Morbidity at bone graft donor sites. J Orthop Trauma 3:192–195CrossRefPubMed

29.

Jansen JA, Vehof JW, Ruhe PQ, Kroeze-Deutman H, Kuboki Y, Takita H, Hedberg EL, Mikos AG (2005) Growth factor-loaded scaffolds for bone engineering. J Control Release 101:127–136CrossRefPubMed

30.

Oest ME, Dupont KM, Kong HJ, Mooney DJ, Guldberg RE (2007) Quantitative assessment of scaffold and growth factor-mediated repair of critically sized bone defects. J Orthop Res 25:941–950CrossRefPubMed

31.

Gao C, Deng Y, Feng P, Mao Z, Li P, Yang B, Deng J, Cao Y, Shuai C, Peng S (2014) Current progress in bioactive ceramic scaffolds for bone repair and regeneration. Int J Mol Sci 15:4714–4732CrossRefPubMedPubMedCentral

32.

Lieberman JR, Daluiski A, Einhorn TA (2002) The role of growth factors in the repair of bone. Biology and clinical applications. J Bone Joint Surg Am 84:1032–1044

33.

Park J, Ries J, Gelse K, Kloss F, von der Mark K, Wiltfang J, Neukam FW, Schneider H (2003) Bone regeneration in critical size defects by cell-mediated BMP-2 gene transfer: a comparison of adenoviral vectors and liposomes. Gene Ther 10:1089–1098CrossRefPubMed

34.

Lian JB, Stein GS (2003) Runx2/Cbfa1: a multifunctional regulator of bone formation. Curr Pharm Des 9:2677–2685CrossRefPubMed

35.

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

36.

Sinha KM, Zhou X (2013) Genetic and molecular control of osterix in skeletal formation. J Cell Biochem 114:975–984CrossRefPubMedPubMedCentral

37.

Aubin JE (2001) Regulation of osteoblast formation and function. Rev Endocr Metab Disord 2:81–94CrossRefPubMed

38.

Bruderer M, Richards RG, Alini M, Stoddart MJ (2014) Role and regulation of RUNX2 in osteogenesis. Eur Cell Mater 28:269–286CrossRefPubMed

39.

Bais MV, Wigner N, Young M, Toholka R, Graves DT, Morgan EF, Gerstenfeld LC, Einhorn TA (2009) BMP2 is essential for post natal osteogenesis but not for recruitment of osteogenic stem cells. Bone 45:254–266CrossRefPubMedPubMedCentral

40.

Chen G, Deng C, Li YP (2012) TGF-beta and BMP signaling in osteoblast differentiation and bone formation. Int J Biol Sci 8:272–288CrossRefPubMedPubMedCentral

41.

Jeon EJ, Lee KY, Choi NS, Lee MH, Kim HN, Jin YH, Ryoo HM, Choi JY, Yoshida M, Nishino N, Oh BC, Lee KS, Lee YH, Bae SC (2006) Bone morphogenetic protein-2 stimulates Runx2 acetylation. J Biol Chem 281:16502–165011CrossRefPubMed

42.

Wu Y, Wang J, Scott PG, Tredget EE (2007) Bone marrow-derived stem cells in wound healing: a review. Wound Repair Regen 15:S18–S26CrossRefPubMed

43.

Kumar S, Ponnazhagan S (2012) Mobilization of bone marrow mesenchymal stem cells in vivo augments bone healing in a mouse model of segmental bone defect. Bone 50:1012–1018CrossRefPubMedPubMedCentral

44.

Gillis P, Savla U, Volpert OV, Jimenez B, Waters CM, Panos RJ, Bouck NP (1999) Keratinocyte growth factor induces angiogenesis and protects endothelial barrier function. J Cell Sci 112:2049–2057PubMed

45.

Yao L, Liu CJ, Luo Q, Gong M, Chen J, Wang LJ, Huang Y, Jiang X, Xu F, Li TY, Shu C (2013) Protection against hyperoxia-induced lung fibrosis by KGF-induced MSCs mobilization in neonatal rats. Pediatr Transplant 17:676–682PubMed

46.

Pawig L, Klasen C, Weber C, Bernhagen J, Noels H (2015) Diversity and inter-connections in the CXCR4 chemokine receptor/ligand family: molecular perspectives. Front Immunol 6:429CrossRefPubMedPubMedCentral

47.

Khorramdelazad H, Bagheri V, Hassanshahi G, Zeinali M, Vakilian A (2016) New insights into the role of stromal cell-derived factor 1 (SDF-1/CXCL12) in the pathophysiology of multiple sclerosis. J Neuroimmunol 290:70–75CrossRefPubMed

48.

Chang L, Karin M (2001) Mammalian MAP kinase signaling cascades. Nature 410:37–40CrossRefPubMed

49.

Eswarakumar VP, Lax I, Schlessinger J (2005) Cellular signaling by fibroblast growth factor receptors. Cytokine Growth Factor Rev 16:139–149CrossRefPubMed

50.

Liedert A, Kaspar D, Blakytny R, Claes L, Ignatius A (2006) Signal transduction pathways involved in mechanotransduction in bone cells. Biochem Biophys Res Commun 349:1–5CrossRefPubMed

51.

Ahn HJ, Lee WJ, Kwack K, Kwon YD (2009) FGF2 stimulates the proliferation of human mesenchymal stem cells through the transient activation of JNK signaling. FEBS Lett 583:2922–2926CrossRefPubMed

52.

Papachristou DJ, Pirttiniemi P, Kantomaa T, Papavassiliou AG, Basdra EK (2005) JNK/ERK-AP-1/Runx2 induction ‘‘paves the way’’ to cartilage load-ignited chondroblastic differentiation. Histochem Cell Biol 124:215–223CrossRefPubMed

53.

Kanno T, Takahashi T, Tsujisawa T, Ariyoshi W, Nishihara T (2007) Mechanical stress-mediated Runx2 activation is dependent on Ras/ERK1/2 MAPK signaling in osteoblasts. J Cell Biochem 101:1266–1277CrossRefPubMed

Titel: Local delivery of recombinant human FGF7 enhances bone formation in rat mandible defects
verfasst von: Sher Bahadur Poudel
Govinda Bhattarai
Jae-Hwan Kim
Sung-Ho Kook
Young-Kwon Seo
Young-Mi Jeon
Jeong-Chae Lee
Publikationsdatum: 20.10.2016
Verlag: Springer Japan
Erschienen in: Journal of Bone and Mineral Metabolism / Ausgabe 5/2017
Print ISSN: 0914-8779
Elektronische ISSN: 1435-5604
DOI: https://doi.org/10.1007/s00774-016-0784-5

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

Echinokokkose medikamentös behandeln oder operieren?

06.05.2024 DCK 2024 Kongressbericht

Die Therapie von Echinokokkosen sollte immer in spezialisierten Zentren erfolgen. Eine symptomlose Echinokokkose kann – egal ob von Hunde- oder Fuchsbandwurm ausgelöst – konservativ erfolgen. Wenn eine Op. nötig ist, kann es sinnvoll sein, vorher Zysten zu leeren und zu desinfizieren.

Aquatherapie bei Fibromyalgie wirksamer als Trockenübungen

03.05.2024 Fibromyalgiesyndrom Nachrichten

Bewegungs-, Dehnungs- und Entspannungsübungen im Wasser lindern die Beschwerden von Patientinnen mit Fibromyalgie besser als das Üben auf trockenem Land. Das geht aus einer spanisch-brasilianischen Vergleichsstudie hervor.

Wo hapert es noch bei der Umsetzung der POMGAT-Leitlinie?

03.05.2024 DCK 2024 Kongressbericht

Seit November 2023 gibt es evidenzbasierte Empfehlungen zum perioperativen Management bei gastrointestinalen Tumoren (POMGAT) auf S3-Niveau. Vieles wird schon entsprechend der Empfehlungen durchgeführt. Wo es im Alltag noch hapert, zeigt eine Umfrage in einem Klinikverbund.

Das Risiko für Vorhofflimmern in der Bevölkerung steigt

02.05.2024 Vorhofflimmern Nachrichten

Das Risiko, im Lauf des Lebens an Vorhofflimmern zu erkranken, ist in den vergangenen 20 Jahren gestiegen: Laut dänischen Zahlen wird es drei von zehn Personen treffen. Das hat Folgen weit über die Schlaganfallgefährdung hinaus.

Update Innere Medizin

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

Newsletter bestellen

Live-Webinar "Chronische Unterbauch- und Viszeralschmerzen in der Praxis managen"

Springer Medizin

Abstract

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

Weitere Artikel der Ausgabe 5/2017

Comparison of the effects of denosumab between a native vitamin D combination and an active vitamin D combination in patients with postmenopausal osteoporosis

Body composition analysis by DXA (dual X-ray absorptiometry) in Brazilian men: normative data

The effects of P-gp and CYP450 modulated by rifampicin on the steroid-induced osteonecrosis of the femoral head

Vitamin K homologs as potential biomarkers for disease activity in patients with rheumatoid arthritis

Low calcium and vitamin D intake in Korean women over 50 years of age