Blockade of the hedgehog pathway inhibits osteophyte formation in arthritis.

Ruiz-Heiland G, Horn A, Zerr P, Hofstetter W, Baum W, Stock M, Distler J, Nimmerjahn F, Schett G, Zwerina J (2012)

Publication Status: Published

Publication Type: Journal article

Publication year: 2012

Journal

Annals of the Rheumatic Diseases BMJ Publishing Group

Book Volume: 71

Pages Range: 400-7

Journal Issue: 3

DOI: 10.1136/ard.2010.148262

Abstract

BACKGROUND\nOsteophyte formation is a common phenomenon in arthritis. Bone formation by endochondral ossification is considered a key pathophysiological process in the formation of osteophytes.\nOBJECTIVE\nTo examine the hypothesis that inhibition of smoothened (Smo), a key component of the hedgehog pathway inhibits osteophyte formation as the hedgehog pathway mediates endochondral ossification.\nMETHODS\nArthritis was induced in 8-week-old C57/BL6 mice by serum transfer (K/BxN model). Mice were then treated by daily administration of either vehicle or LDE223, a specific small molecule inhibitor for Smo, over 2 weeks starting at the onset of disease. Clinical course of arthritis, histological and molecular changes of bone in the affected joints as well as systemic bone changes were assessed.\nRESULTS\nSerum transfer-induced arthritis led to severe osteophyte formation within 2 weeks of onset. Blockade of Smo inhibited hedgehog signalling in vivo and also significantly inhibited osteophyte formation, whereas the clinical and histopathological signs of arthritis were not affected. Also, systemic bone mass did not change. Smo inhibitor particularly blocked the formation of hypertrophic chondrocytes and collagen type X expression.\nCONCLUSIONS\nThe data indicate that blockade of hedgehog signalling by targeting Smo specifically inhibits osteophyte formation in arthritis without affecting inflammation and without eliciting bone destruction at the local and systemic level. Blockade of Smo may thus be considered as a strategy to specifically influence the periosteal bone response in arthritis associated with bone apposition.

Authors with CRIS profile

Angelika Horn Medizinische Fakultät Pawel Zerr Department of Medicine 3 – Rheumatology and Immunology Michael Stock Department of Medicine 3 – Rheumatology and Immunology Jörg Distler Professur für Molekulare Mechanismen der Organfibrose Falk Nimmerjahn Lehrstuhl für Genetik Georg Schett Lehrstuhl für Innere Medizin III

Involved external institutions

Universität Bern CH Switzerland (CH)

How to cite

APA:

Ruiz-Heiland, G., Horn, A., Zerr, P., Hofstetter, W., Baum, W., Stock, M.,... Zwerina, J. (2012). Blockade of the hedgehog pathway inhibits osteophyte formation in arthritis. Annals of the Rheumatic Diseases, 71(3), 400-7. https://doi.org/10.1136/ard.2010.148262

MLA:

Ruiz-Heiland, Gisela, et al. "Blockade of the hedgehog pathway inhibits osteophyte formation in arthritis." Annals of the Rheumatic Diseases 71.3 (2012): 400-7.

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