Survey Proteases and bone remodelling S. Georges a,b , C. Ruiz Velasco a,b , V. Trichet a,b , Y. Fortun a,b,c , D. Heymann a,b,d , M. Padrines a,b, * a Universite ´ de Nantes, Nantes Atlantique Universite ´s, Laboratoire de Physiopathologie de la Re ´sorption Osseuse et The ´rapie des Tumeurs Osseuses Primitives, EA 3822, Nantes F-44035 France b INSERM, ERI 7, Nantes F-44035, France c Universite ´ d’Angers, IUT, France d Centre Hospitalier Universitaire de Nantes, France Available online 28 November 2008 Abstract Bone remodelling is regulated by osteogenic cells which act individually through cellular and molecular interaction. These interactions can be established either through a cell–cell contact, involving molecules of the integrin family, or by the release of many polypeptidic factors and/or their soluble receptor chains. Proteolytic shedding of membrane-associated proteins regulates the physiological activity of numerous proteins. Proteases located on the plasma membrane, either as transmembrane proteins or anchored to cell-surface molecules, serve as activators or inhibitors of different cellular and physiological processes. This review will focus on the role of the proteases implicated in bone remodelling either through the proteolytic degradation of the extracellular matrix or through their relations with osteogenic factors. Their implication in bone tumor progression will be also considered. # 2008 Elsevier Ltd. All rights reserved. Keywords: Protease; Bone remodelling; Cathepsin K; Metalloproteinases Contents 1. Introduction ............................................................................... 29 2. Cathepsin K ............................................................................... 30 3. Metalloproteinases ........................................................................... 32 4. Metalloproteinases and bone matrix ............................................................... 32 5. Metalloproteinases, growth factors and cytokines ...................................................... 34 6. Metalloproteinases and bone tumor ............................................................... 36 Acknowledgements .......................................................................... 38 References ................................................................................ 39 1. Introduction Bone-forming and bone-resorbing cells are closely associated in time and space. Indeed, following a bone stimulus (mechanical load, hormones, growth factors), osteoclastic cells are recruited at the bone surface and thus degrade bone mineral components by an acid extracellular mechanism called resorption phase. The osteogenic cells (osteoclasts, osteoblasts) contribute individually to the bone remodelling whereas their interactions control their cellular activities as well as the intensity of the bone remodelling. These interactions can be established either through a cell to cell contact or by the release of many polypeptidic factors www.elsevier.com/locate/cytogfr Available online at www.sciencedirect.com Cytokine & Growth Factor Reviews 20 (2009) 29–41 * Corresponding author at: EA 3822, INSERM ERI 7, Faculte ´ de Me ´de- cine, 1 rue Gaston Veil, 44035 Nantes Cedex 01, France. Tel.: +33 240 412 846; fax: +33 240 412 860. E-mail address: marc.padrines@univ-nantes.fr (M. Padrines). 1359-6101/$ – see front matter # 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.cytogfr.2008.11.005