Einzeltreffer — DigiBib

Acquired heterotopic ossification (HO) is a painful and debilitating disease characterized by extraskeletal bone formation after injury. The exact pathogenesis of HO remains unknown. Here we show that TGF-β initiates and promotes HO in mice. We find that calcified cartilage and newly formed bone resorb osteoclasts after onset of HO, which leads to high levels of active TGF-β that recruit mesenchymal stromal/progenitor cells (MSPCs) in the HO microenvironment. Transgenic expression of active TGF-β in tendon induces spontaneous HO, whereas systemic injection of a TGF-β neutralizing antibody attenuates ectopic bone formation in traumatic and BMP-induced mouse HO models, and in a fibrodysplasia ossificans progressive mouse model. Moreover, inducible knockout of the TGF-β type II receptor in MSPCs inhibits HO progression in HO mouse models. Our study points toward elevated levels of active TGF-β as inducers and promoters of ectopic bone formation, and suggest that TGF-β might be a therapeutic target in HO.

Titel:	Inhibition of overactive TGF-β attenuates progression of heterotopic ossification in mice.
Autor/in / Beteiligte Person:	Wang, X ; Li, F ; Xie, L ; Crane, J ; Zhen, G ; Mishina, Y ; Deng, R ; Gao, B ; Chen, H ; Liu, S ; Yang, P ; Gao, M ; Tu, M ; Wang, Y ; Wan, M ; Fan, C ; Cao, X
Link:	Zum Volltext
Zeitschrift:	Nature communications, Jg. 9 (2018-02-07), Heft 1, S. 551
Veröffentlichung:	[London] : Nature Pub. Group, 2018
Medientyp:	academicJournal
ISSN:	2041-1723 (electronic)
DOI:	10.1038/s41467-018-02988-5
Schlagwort:	Achilles Tendon drug effects Achilles Tendon injuries Adult Animals Antibodies, Neutralizing pharmacology Becaplermin metabolism Bone Remodeling Brain Injuries, Traumatic Cartilage Case-Control Studies Disease Models, Animal Elbow Joint surgery Female Fracture Fixation, Internal Fractures, Bone Humans Male Mesenchymal Stem Cells metabolism Mice Mice, Knockout Mice, Transgenic Middle Aged Muscle, Skeletal pathology Myositis Ossificans metabolism Osteogenesis drug effects Receptor, Transforming Growth Factor-beta Type II genetics Spinal Cord Injuries Tendon Injuries Tendons Transforming Growth Factor beta antagonists & inhibitors Transforming Growth Factor beta1 metabolism Young Adult Elbow Injuries Ossification, Heterotopic metabolism Osteoclasts Transforming Growth Factor beta metabolism
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, N.I.H., Extramural Language: English [Nat Commun] 2018 Feb 07; Vol. 9 (1), pp. 551. <i>Date of Electronic Publication: </i>2018 Feb 07. MeSH Terms: Osteoclasts* ; Ossification, Heterotopic / metabolism ; Transforming Growth Factor beta / metabolism ; Achilles Tendon / drug effects ; Achilles Tendon / injuries ; Adult ; Animals ; Antibodies, Neutralizing / pharmacology ; Becaplermin / metabolism ; Bone Remodeling ; Brain Injuries, Traumatic ; Cartilage ; Case-Control Studies ; Disease Models, Animal ; Elbow Joint / surgery ; Female ; Fracture Fixation, Internal ; Fractures, Bone ; Humans ; Male ; Mesenchymal Stem Cells / metabolism ; Mice ; Mice, Knockout ; Mice, Transgenic ; Middle Aged ; Muscle, Skeletal / pathology ; Myositis Ossificans / metabolism ; Osteogenesis / drug effects ; Receptor, Transforming Growth Factor-beta Type II / genetics ; Spinal Cord Injuries ; Tendon Injuries ; Tendons ; Transforming Growth Factor beta / antagonists & inhibitors ; Transforming Growth Factor beta1 / metabolism ; Young Adult ; Elbow Injuries References: Spinal Cord. 2002 Jul;40(7):313-26. (PMID: 12080459) ; J Immunol Methods. 2014 Jun;408:89-100. (PMID: 24857755) ; J Clin Invest. 2014 Feb;124(2):466-72. (PMID: 24487640) ; Semin Nephrol. 2007 May;27(3):309-20. (PMID: 17533008) ; Cancer Metastasis Rev. 2012 Dec;31(3-4):553-68. (PMID: 22714591) ; Injury. 2011 Aug;42(8):833-7. (PMID: 21529804) ; Genesis. 2002 Feb;32(2):73-5. (PMID: 11857781) ; Cell Res. 2009 Jan;19(1):89-102. (PMID: 19050696) ; N Engl J Med. 2006 Aug 24;355(8):788-98. (PMID: 16928994) ; J Rehabil Med. 2005 May;37(3):129-36. (PMID: 16040468) ; Int J Exp Pathol. 2012 Oct;93(5):319-31. (PMID: 22974213) ; Nat Med. 2014 Nov;20(11):1270-8. (PMID: 25282358) ; Sci Transl Med. 2016 Nov 23;8(366):366ra163. (PMID: 27881824) ; Nat Genet. 2005 Mar;37(3):275-81. (PMID: 15731757) ; Genes Dis. 2014 Sep;1(1):87-105. (PMID: 25401122) ; Trends Pharmacol Sci. 2014 May;35(5):227-36. (PMID: 24745631) ; Nat Med. 2013 Jun;19(6):704-12. (PMID: 23685840) ; J Immunol. 2014 May 15;192(10 ):4560-4570. (PMID: 24711618) ; Nat Genet. 2006 May;38(5):525-7. (PMID: 16642017) ; Cell Tissue Res. 2012 Jan;347(1):245-56. (PMID: 22006249) ; J Comp Neurol. 2004 Feb 9;469(3):311-24. (PMID: 14730584) ; J Orthop Surg Res. 2009 Apr 20;4:12. (PMID: 19379483) ; J Bone Miner Res. 2010 May;25(5):1147-56. (PMID: 19839764) ; Nature. 2011 Jun 15;474(7351):343-9. (PMID: 21677751) ; J Pathol. 1983 Apr;139(4):419-30. (PMID: 6220140) ; Stem Cells. 2012 Nov;30(11):2498-511. (PMID: 22911900) ; J Histochem Cytochem. 2010 Aug;58(8):721-30. (PMID: 20421592) ; Genesis. 2006 Apr;44(4):159-67. (PMID: 16604518) ; Am J Pathol. 2004 Jul;165(1):203-17. (PMID: 15215176) ; Nature. 2010 Aug 12;466(7308):829-34. (PMID: 20703299) ; Nature. 2016 Apr 21;532(7599):323-8. (PMID: 27074509) ; Osteoarthritis Cartilage. 2009 Dec;17 (12 ):1539-45. (PMID: 19583961) ; Cell Stem Cell. 2014 Aug 7;15(2):154-68. (PMID: 24953181) ; Science. 1988 Dec 16;242(4885):1528-34. (PMID: 3201241) ; Nat Med. 2008 Dec;14(12):1363-9. (PMID: 19029982) ; Pediatr Endocrinol Rev. 2013 Jun;10 Suppl 2:437-48. (PMID: 23858627) ; J Nucl Med. 2002 Mar;43(3):346-53. (PMID: 11884494) ; Nat Rev Rheumatol. 2010 Sep;6(9):518-27. (PMID: 20703219) ; Orthopedics. 2011 Mar 11;34(3):177. (PMID: 21410128) ; J Immunol. 1989 Mar 1;142(5):1536-41. (PMID: 2537357) ; N Engl J Med. 2000 May 4;342(18):1350-8. (PMID: 10793168) ; Nat Med. 2015 Nov;21(11):1262-1271. (PMID: 26457758) ; Nat Med. 2011 Apr;17(4):454-60. (PMID: 21460849) ; Nat Genet. 2000 Nov;26(3):273-5. (PMID: 11062463) ; Nat Protoc. 2007;2(10):2480-91. (PMID: 17947990) ; Nat Med. 2009 Jul;15(7):757-65. (PMID: 19584867) ; N Engl J Med. 2002 Jan 10;346(2):99-106. (PMID: 11784876) ; Int Orthop. 2015 Dec;39(12 ):2495-501. (PMID: 26432574) ; Dev Cell. 2014 May 12;29(3):330-9. (PMID: 24823376) ; Exp Cell Res. 1992 Jan;198(1):130-4. (PMID: 1309194) ; Am J Respir Cell Mol Biol. 2008 Nov;39(5):499-502. (PMID: 18927350) ; Nat Genet. 2004 Aug;36(8):855-60. (PMID: 15235604) ; Semin Liver Dis. 2010 Aug;30(3):245-57. (PMID: 20665377) ; Nature. 2014 Mar 20;507(7492):323-328. (PMID: 24646994) ; J Orthop Trauma. 2016 Oct;30 Suppl 3:S27-S30. (PMID: 27661424) ; J Cell Sci. 2003 Jan 15;116(Pt 2):217-24. (PMID: 12482908) ; Transgenic Res. 1999 Aug;8(4):265-77. (PMID: 10621974) ; Nat Rev Rheumatol. 2011 Jan;7(1):43-9. (PMID: 21135881) ; Nat Med. 2014 Jun;20(6):670-5. (PMID: 24793237) ; J Bone Miner Res. 2012 Aug;27(8):1619-22. (PMID: 22806925) ; Bone. 2016 Mar;84:169-80. (PMID: 26769004) ; Nat Med. 2010 Dec;16(12):1400-6. (PMID: 21102460) ; Nat Med. 2012 Jul;18(7):1095-101. (PMID: 22729283) ; J Am Acad Orthop Surg. 1994 Oct;2(5):288-296. (PMID: 10709021) ; N Engl J Med. 1996 Aug 22;335(8):555-61. (PMID: 8678932) ; Science. 2009 Nov 27;326(5957):1216-9. (PMID: 19965464) ; Cancer Res. 2013 Apr 1;73(7):2333-44. (PMID: 23365134) ; Semin Cell Dev Biol. 2016 Jan;49:30-6. (PMID: 26706149) Grant Information: K08 AR064833 United States AR NIAMS NIH HHS; R01 AR063943 United States AR NIAMS NIH HHS; R01 AR071432 United States AR NIAMS NIH HHS Substance Nomenclature: 0 (Antibodies, Neutralizing) ; 0 (TGFB1 protein, human) ; 0 (Transforming Growth Factor beta) ; 0 (Transforming Growth Factor beta1) ; 1B56C968OA (Becaplermin) ; EC 2.7.11.30 (Receptor, Transforming Growth Factor-beta Type II) Entry Date(s): Date Created: 20180209 Date Completed: 20181211 Latest Revision: 20230813 Update Code: 20240513 PubMed Central ID: PMC5803194

Klicken Sie ein Format an und speichern Sie dann die Daten oder geben Sie eine Empfänger-Adresse ein und lassen Sie sich per Email zusenden.

BibTeX Citavi, JabRef, u.a.
(Literaturverwaltung)

PDF kein Volltext!
(Merkzettel, Notizen)

RIS Endnote, Citavi u.a.
(Literaturverwaltung)

MODS
(XML zur Weiterverarbeitung)

oder

Wählen Sie das für Sie passende Zitationsformat und kopieren Sie es dann in die Zwischenablage, lassen es sich per Mail zusenden oder speichern es als PDF-Datei.

Gewünschter Zitations-Stil:

oder

Bitte prüfen Sie, ob die Zitation formal korrekt ist, bevor Sie sie in einer Arbeit verwenden. Benutzen Sie gegebenenfalls den "Exportieren"-Dialog, wenn Sie ein Literaturverwaltungsprogramm verwenden und die Zitat-Angaben selbst formatieren wollen.

Inhibition of overactive TGF-β attenuates progression of heterotopic ossification in mice.