Print Email Facebook Twitter Cathepsin K is the principal protease in giant cell tumor of bone Title Cathepsin K is the principal protease in giant cell tumor of bone Author Lindeman, J.H.N. Hanemaaijer, R. Mulder, A. Dijkstra, P.D.S. Szuhai, K. Bromme, D. Verheijen, J.H. Hogendoorn, P.C.W. Publication year 2004 Abstract Giant cell tumor (GCT) of bone is a neoplasm of bone characterized by a localized osteolytic lesion. The nature of GCT is an enigma and the cell type(s) and protease(s) responsible for the extensive localized clinicoradiological osteolysis remain unresolved. We evaluated protease expression and cellular distribution of the proteolytic machinery responsible for the osteolysis. mRNA profiles showed that cathepsin K, cathepsin L, and matrix metalloproteinase (MMP)-9 were the preferentially expressed collagenases. Moderate expression was found for MMP-13, MMP-14, and cathepsin S. Specific protease activity assays revealed high cathepsin K activity but showed that MMP-9 was primarily present (98%) as inactive proenzyme. Activities of MMP-13 and MMP-14 were low. Immunohistochemistry revealed a clear spatial distribution: cathepsin K, its associated proton pump V-H+-ATPase, and MMP-9 were exclusively expressed in osteoclast-like giant cells, whereas cathepsin L expression was confined to mononuclear cells. To explore a possible role of cathepsin L in osteolysis, GCT-derived, cathepsin L-expressing, mononuclear cells were cultured on dentine disks. No evidence of osteolysis by these cells was found. These results implicate cathepsin K as the principal protease in GCT and suggest that osteoclast-like giant cells are responsible for the osteolysis. Inhibition of cathepsin K or its associated proton-pump may provide new therapeutic opportunities for GCT. Chemicals / CAS: cathepsin K, 94716-09-3; cathepsin L, 60616-82-2; cathepsin S, 71965-46-3; collagen, 9007-34-5; collagenase 3, 175449-82-8; gelatinase B, 146480-36-6; proteinase, 9001-92-7; cathepsin K, EC 3.4.22.-; cathepsin L, EC 22.214.171.124; cathepsin S, EC 126.96.36.199; Cathepsins, EC 3.4.-; Collagenases, EC 3.4.24.-; Cysteine Endopeptidases, EC 3.4.22.-; Matrix Metalloproteinase 13, EC 3.4.24.-; Matrix Metalloproteinases, Membrane-Associated, EC 3.4.24.-; Metalloendopeptidases, EC 3.4.24.-; MMP13 protein, human, EC 3.4.24.-; RNA, Messenger Subject HealthCathepsin KCathepsin LCathepsin SCollagenCollagenase 3Gelatinase BMatrix metalloproteinase 14Messenger RNAProteinaseBone tumorClinical articleEnzyme activityHuman tissueImmunohistochemistryMetaphysisOsteolysisProtein expressionReal time polymerase chain reactionAdultBone NeoplasmsCathepsinsCollagenasesCysteine EndopeptidasesFemaleGiant Cell Tumor of BoneHumansImmunoenzyme TechniquesMaleMatrix Metalloproteinase 13Matrix Metalloproteinases, Membrane-AssociatedMetalloendopeptidasesMiddle AgedOsteoclastsOsteolysisRNA, Messenger To reference this document use: http://resolver.tudelft.nl/uuid:e4084910-e76d-4a20-9c10-ac34f0ae94d4 TNO identifier 237911 ISSN 0002-9440 Source American Journal of Pathology, 165 (2), 593-600 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.