Cysteine Cathepsins and the Skeleton

vonder Mark K. Structure and biosynthesis of collagens. In: Seibel M, Robins S, Bilezikian J, editors. San Diego: Academic Press; 1999. Robins S. Fibrillogenesis and maturation of collagens in Dynamics of bone and cartilage metabolism. In: Seiber M, Robins S, Bilezikian J, editors. San Diego: Academic Press; 1999. Reynolds JJ. Collagenases and tissue inhibitors of metalloproteinases: a functional balance in tissue degradation. Oral Dis. 1996;2:70–6. Mookhtiar KA, et al. Clostridium histolyticum collagenases: a new look at some old enzymes. Matrix Suppl. 1992;1:116–26. Brömme D, et al. Human cathepsin O2, a matrix protein-degrading cysteine protease expressed in osteoclasts. Functional expression of human cathepsin O2 in Spodoptera frugiperda and characterization of the enzyme. J Biol Chem. 1996;271:2126–32. French MF, et al. Identification of Clostridium histolyticum collagenase hyperreactive sites in type I, II, and III collagens: lack of correlation with local triple helical stability. J Protein Chem. 1992;11:83–97. Garnero P, et al. The collagenolytic activity of cathepsin K is unique among mammalian proteinases. J Biol Chem. 1998;273:32347–52. Burleigh MC, et al. Cathepsin B1. A lysosomal enzyme that degrades native collagen. Biochem J. 1974;137:387–98. Etherington DJ, et al. The action of cathepsin B and collagenolytic cathepsin in the degradation of collagen. Acta Biol Med Ger. 1977;36:1555–63. Gal S, et al. The major excreted protein of transformed fibroblasts is an activable acid-protease. J Biol Chem. 1986;261:1760–5. Tezuka K, et al. Molecular cloning of a possible cysteine proteinase predominantly expressed in osteoclasts. J Biol Chem. 1994;269:1106–9. Bossard MJ, et al. Proteolytic activity of human osteoclast cathepsin K. Expression, purification, activation, and substrate identification. J Biol Chem. 1996;271:12517–24. Willstaetter R, et al. Ueber die Proteasen der Magenschleimhaut. Hoppe-Seyler’s Z Physiol Chem. 1929;180:127–43. Mason RW. Emerging functions of placental cathepsins. Placenta. 2008;29:385–90. Wiederanders B, et al. Functions of propeptide parts in cysteine proteases. Curr Protein Pept Sci. 2003;4:309–26. Polgar L, et al. Current problems in mechanistic studies of serine and cysteine proteinases. Biochem J. 1982;207:1–10. Mellor GW, et al. Ionization characteristics of the Cys-25/His-159 interactive system and of the modulatory group of papain: resolution of ambiguity by electronic perturbation of the quasi-2-mercaptopyridine leaving group in a new pyrimidyl disulphide reactivity probe. Biochem J. 1993;290(Pt 1):289–96. Musil D, et al. The refined 2.15 A X-ray crystal structure of human liver cathepsin B: the structural basis for its specificity. EMBO J. 1991;10:2321–30. Guncar G, et al. Crystal structure of MHC class II-associated p41 Ii fragment bound to cathepsin L reveals the structural basis for differentiation between cathepsins L and S. EMBO J. 1999;18:793–803. McGrath ME, et al. Crystal structure of human cathepsin K complexed with a potent inhibitor. Nat Struct Biol. 1997;4:105–9. McGrath ME, et al. Crystal structure of human cathepsin S. Protein Sci. 1998;7:1294–302. Somoza JR, et al. Crystal structure of human cathepsin V. Biochemistry. 2000;39:12543–51. Somoza JR, et al. The crystal structure of human cathepsin F and its implications for the development of novel immunomodulators. J Mol Biol. 2002;322:559–68. Guncar G, et al. Crystal structure of porcine cathepsin H determined at 2.1 A resolution: location of the mini-chain C-terminal carboxyl group defines cathepsin H aminopeptidase function. Structure. 1998;6:51–61. Guncar G, et al. Crystal structure of cathepsin X: a flip-flop of the ring of His23 allows carboxy-monopeptidase and carboxy-dipeptidase activity of the protease. Structure. 2000;8:305–13. Molgaard A, et al. The crystal structure of human dipeptidyl peptidase I (cathepsin C) in complex with the inhibitor Gly-Phe-CHN2. Biochem J. 2007;401:645–50. Riese RJ, et al. Cathepsins and compartmentalization in antigen presentation. Curr Opin Immunol. 2000;12:107–13. Shi GP, et al. Role for cathepsin F in invariant chain processing and major histocompatibility complex class II peptide loading by macrophages. J Exp Med. 2000;191:1177–86. Tolosa E, et al. Cathepsin V is involved in the degradation of invariant chain in human thymus and is overexpressed in myasthenia gravis. J Clin Invest. 2003;112:517–26. Pham CT, et al. Dipeptidyl peptidase I is required for the processing and activation of granzymes A and B in vivo. Proc Natl Acad Sci USA. 1999;96:8627–32. Linnevers C, et al. Human cathepsin W, a putative cysteine protease predominantly expressed in CD8 + T-lymphocytes. FEBS Lett. 1997;405:253–9. Wex T, et al. Human cathepsin W, a cysteine protease predominantly expressed in NK cells, is mainly localized in the endoplasmic reticulum. J Immunol. 2001;167:2172–8. Velasco G, et al. Human cathepsin O. Molecular cloning from a breast carcinoma, production of the active enzyme in Escherichia coli, and expression analysis in human tissues. J Biol Chem. 1994;269:27136–42. Bromme D, et al. Human cathepsin O2, a novel cysteine protease highly expressed in osteoclastomas and ovary molecular cloning, sequencing and tissue distribution. Biol Chem Hoppe Seyler. 1995;376:379–84. Drake FH, et al. Cathepsin K, but not cathepsins B, L, or S, is abundantly expressed in human osteoclasts. J Biol Chem. 1996;271:12511–6. Hou WS, et al. Cathepsin K is a critical protease in synovial fibroblast-mediated collagen degradation. Am J Pathol. 2001;159:2167–77. Hou W-S, et al. Comparison of cathepsins K and S expression within the rheumatoid and osteoarthritic synovium. Arthritis Rheum. 2002;46:663–74. Tepel C, et al. Cathepsin K in thyroid epithelial cells: sequence, localization and possible function in extracellular proteolysis of thyroglobulin. J Cell Sci. 2000;113:4487–98. Buhling F, et al. Cathepsin K expression in human lung. Adv Exp Med Biol. 2000;477:281–6. Buhling F, et al. Cathepsin K–a marker of macrophage differentiation? J Pathol. 2001;195:375–82. Everts V, et al. Phagocytosis and intracellular digestion of collagen, its role in turnover and remodeling. Histochem J. 1996;28:229–45. Everts V, et al. The digestion of phagocytosed collagen is inhibited by the proteinase inhibitors leupeptin and E-64. Coll Relat Res. 1985;5:315–36. Kirschke H, et al. Cathepsin S. The cysteine proteinase from bovine lymphoid tissue is distinct from cathepsin L (EC 3.4.22.15). Biochem J. 1986;240:455–9. Bromme D, et al. Functional expression of human cathepsin S in Saccharomyces cerevisiae. Purification and characterization of the recombinant enzyme. J Biol Chem. 1993;268:4832–8. Konttinen YT, et al. Acidic cysteine endoproteinase cathepsin K in the degeneration of the superficial articular hyaline cartilage in osteoarthritis. Arthritis Rheum. 2002;46:953–60. Rozhin J, et al. Pericellular pH affects distribution and secretion of cathepsin B in malignant cells. Cancer Res. 1994;54:6517–25. Xia L, et al. Localization of rat cathepsin K in osteoclasts and resorption pits: Inhibition of bone resorption cathepsin K-activity by peptidyl vinyl sulfones. Biol Chem. 1999;380:679–87. Vasiljeva O, et al. Recombinant human procathepsin S is capable of autocatalytic processing at neutral pH in the presence of glycosaminoglycans. FEBS Lett. 2005;579:1285–90. Pungercar JR, et al. Autocatalytic processing of procathepsin B is triggered by proenzyme activity. Febs J. 2009;276:660–8. Reddy VY, et al. Pericellular mobilization of the tissue-destructive cysteine proteinases, cathepsins B, L, and S, by human monocyte-derived macrophages. Proc Natl Acad Sci USA. 1995;92:3849–53. Jordans S, et al. Monitoring compartment-specific substrate cleavage by cathepsins B, K, L, and S at physiological pH and redox conditions. BMC Biochem. 2009;10:23. Godat E, et al. Regulation of cathepsin K activity by hydrogen peroxide. Biol Chem. 2008;389:1123–6. Buttle DJ, et al. Lysosomal cysteine endopeptidases mediate interleukin 1-stimulated cartilage proteoglycan degradation. Biochem J. 1992;287:657–61. Li Q, et al. Gamma interferon induced increases in intracellular cathepsin B activity in PMA primed THP-1 cells are blocked by inhibitors of protein kinase C. Immunopharmacol Immunotoxicol. 1996;18:375–96. Storm van’s Gravesande K, et al. IFN regulatory factor-1 regulates IFN-gamma-dependent cathepsin S expression. J Immunol. 2002;168:4488–94. Furuyama N, et al. Distinct roles of cathepsin K and cathepsin L in osteoclastic bone resorption. Endocr Res. 2000;26:189–204. Troen BR. The regulation of cathepsin K gene expression. Ann N Y Acad Sci. 2006;1068:165–72. Li Z, et al. Collagenolytic activity of cathepsin K is specifically modulated by cartilage-resident chondroitin sulfates. Biochemistry. 2000;39:529–36. Li Z, et al. Collagenase activity of cathepsin K depends on complex formation with chondroitin sulfate. J Biol Chem. 2002;277:28669–76. Li Z, et al. Regulation of collagenase activities of human cathepsins by glycosaminoglycans. J Biol Chem. 2004;279:5470–9. Li Z, et al. The crystal and molecular structures of a cathepsin K: chondroitin sulfate complex. J Mol Biol. 2008;383:78–91. Cherney MM et al. Activity and structure of cathepsin K variant M5 in complex with chondroitin sulfate. 2010. Neufeld EF. The mucopolysaccharidoses. New YorK: McGraw-Hill; 2001. Wilson S, et al. Glycosaminoglycan-mediated loss of cathepsin K collagenolytic activity in MPS I contributes to osteoclast and growth plate abnormalities. Am J Pathol. 2009;175:2053–62. Wilson SR, et al. Cathepsin K activity-dependent regulation of osteoclast actin ring formation and bone resorption. J Biol Chem. 2009;284:2584–92. Delaisse JM, et al. Mechanism of mineral solubilization and matrix degradation in osteoclastic bone resorption. Boca Raton: CRC Press; 1992. Kafienah W, et al. Human cathepsin K cleaves native type I and II collagens at the N-terminal end of the triple helix. Biochem J. 1998;331:727–32. Gelb BD, et al. Pycnodysostosis, a lysosomal disease caused by cathepsin K deficiency. Science. 1996;273:1236–8. Gelb BD, et al. Pycnodysostosis: cathepsin K deficiency. In: Sriver CR, Beaudet AL, Valle D, Sly WCS, editors. The metabolic and molecular bases of inherited diseases. New York: McGraw-Hill; 2001. p. 3453–68. Everts V, et al. Cathepsin K deficiency in pycnodysostosis results in accumulation of non-digested phagocytosed collagen in fibroblasts. Calcif Tissue Int. 2003;73:380–6. Everts V, et al. Phagocytosis of bone collagen by osteoclasts in two cases of pycnodysostosis. Calcif Tissue Int. 1985;37:25–31. Saftig P, et al. Impaired osteoclastic bone resorption leads to osteopetrosis in cathepsin K-deficient mice. Proc Natl Acad Sci USA. 1998;95:13453–8. Dodds RA, et al. Cathepsin K knockout mice develop osteopetrosis due to lack of full function in their osteoclasts. Bone. 1998;32(Supplement):S164. Hofbauer LC, et al. Osteopetrosis in cathepsin K-deficient mice. Eur J Endocrinol. 1999;140:376–7. Boskey AL, et al. Ablation of cathepsin k activity in the young mouse causes hypermineralization of long bone and growth plates. Calcif Tissue Int. 2009;84:229–39. Kiviranta R, et al. Impaired bone resorption in cathepsin K-deficient mice is partially compensated for by enhanced osteoclastogenesis and increased expression of other proteases via an increased RANKL/OPG ratio. Bone. 2005;36:159–72. Everts V, et al. Functional heterogeneity of osteoclasts: matrix metalloproteinases participate in osteoclastic resorption of calvarial bone but not in resorption of long bone. FASEB J. 1999;13:1219–30. Perez-Amodio S, et al. Calvarial osteoclasts express a higher level of tartrate-resistant acid phosphatase than long bone osteoclasts and activation does not depend on cathepsin K or L activity. Calcif Tissue Int. 2006;79:245–54. Kiviranta R, et al. Accelerated turnover of metaphyseal trabecular bone in mice overexpressing cathepsin K. J Bone Miner Res. 2001;16:1444–52. Mano H, et al. Mammalian mature osteoclasts as estrogen target cells. Biochem Biophys Res Commun. 1996;223:637–42. Parikka V, et al. Estrogen reduces the depth of resorption pits by disturbing the organic bone matrix degradation activity of mature osteoclasts. Endocrinology. 2001;142:5371–8. Furuyama N, et al. Regulation of collagenolytic cysteine protease synthesis by estrogen in osteoclasts. Steroids. 2000;65:371–8. Gay CV, et al. Regulation of differentiated osteoclasts. Crit Rev Eukaryot Gene Expr. 2000;10:213–30. Verzijl N, et al. Effect of collagen turnover on the accumulation of advanced glycation end products. J Biol Chem. 2000;275:39027–31. Goldring SR. Pathogenesis of bone and cartilage destruction in rheumatoid arthritis. Rheumatology. 2003;42(Suppl 2):ii11–6. Malemud CJ. Matrix metalloproteinases: role in skeletal development and growth plate disorders. Front Biosci. 2006;11:1702–15. Baici A, et al. Cathepsin B in osteoarthritis: zonal variation of enzyme activity in human femoral head cartilage. Ann Rheum Dis. 1995;54:281–8. van Noorden CJF, et al. Localization of cathepsin B activity in fibroblasts and chondrocytes by continuous monitoring of the formation of a final fluorescent reaction product using 5-nitrosalicylaldehyde. Histochem J. 1987;19:483–7. Maciewicz RA, et al. Susceptibility of the cartilage collagens types II, IX and XI to degradation by the cysteine proteinases, cathepsins B and L. FEBS Lett. 1990;269:189–93. Mort JS, et al. Cathepsin B: an alternative protease for the generation of an aggrecan’metalloproteinase’ cleavage neoepitope. Biochem J. 1998;335:491–4. Hou WS, et al. Cleavage site specificity of cathepsin K toward cartilage proteoglycans and protease complex formation. Biol Chem. 2003;384:891–7. Buttle DJ. Lysosomal Cysteine Endopeptidases in the degradation of cartilage and bone in immunopharmacology of joints and connective tissue. Academic Press: London; 1994. p. 225–43. Buttle DJ, et al. Inhibition of cartilage proteoglycan release by a specific inactivator of cathepsin B and an inhibitor of matrix metalloproteinases. Evidence for two converging pathways of chondrocyte-mediated proteoglycan degradation. Arthritis Rheum. 1993;36:1709–17. Schedel J, et al. Targeting cathepsin L (CL) by specific ribozymes decreases CL protein synthesis and cartilage destruction in rheumatoid arthritis. Gene Ther. 2004;11:1040–7. Baici A, et al. Cathepsin B in osteoarthritis: cytochemical and histochemical analysis of human femoral head cartilage. Ann Rheum Dis. 1995;54:289–97. Cunnane G, et al. Collagenase, cathepsin B and cathepsin L gene expression in the synovial membrane of patients with early inflammatory arthritis. Rheumatology. 1999;38:34–42. Lemaire R, et al. Selective induction of the secretion of cathepsins B and L by cytokines in synovial fibroblast-like cells. Br J Rheumatol. 1997;36:735–43. Morko JP, et al. Up regulation of cathepsin K expression in articular chondrocytes in a transgenic mouse model for osteoarthritis. Ann Rheum Dis. 2004;63:649–55. Ruettger A, et al. Cathepsins B, K, and L are regulated by a defined collagen type II peptide via activation of classical protein kinase C and p38 MAP kinase in articular chondrocytes. J Biol Chem. 2008;283:1043–51. Dejica VM, et al. Cleavage of type II collagen by cathepsin K in human osteoarthritic cartilage. Am J Pathol. 2008;173:161–9. Vinardell T et al. Evidence to suggest that cathepsin K degrades articular cartilage in naturally occurring equine osteoarthritis. Osteoarthritis Cartilage. 2008. Hummel KM, et al. Cysteine proteinase cathepsin K mRNA is expressed in synovium of patients with rheumatoid arthritis and is detected at sites of synovial bone destruction. J Rheumatol. 1998;25:1887–94. Dodds RA, et al. Expression of cathepsin K messenger RNA in giant cells and their precursors in human osteoarthritic synovial tissues. Arthritis Rheum. 1999;42:1588–93. Salminen-Mankonen HJ, et al. Role of cathepsin K in normal joints and in the development of arthritis. Curr Drug Targets. 2007;8:315–23. Connor JR, et al. Protective effects of a cathepsin K inhibitor, SB-553484, in the canine partial medial meniscectomy model of osteoarthritis. Osteoarthritis Cartilage. 2009;17:1236–43. Morko J, et al. Spontaneous development of synovitis and cartilage degeneration in transgenic mice overexpressing cathepsin K. Arthritis Rheum. 2005;52:3713–7. Schurigt U, et al. Cathepsin K deficiency partially inhibits, but does not prevent, bone destruction in human tumor necrosis factor-transgenic mice. Arthritis Rheum. 2008;58:422–34. Ainola M, et al. Erosive arthritis in a patient with pycnodysostosis: an experiment of nature. Arthritis Rheum. 2008;58:3394–401. Pettit AR, et al. TRANCE/RANKL knockout mice are protected from bone erosion in a serum transfer model of arthritis. Am J Pathol. 2001;159:1689–99. Gravallese EM, et al. Synovial tissue in rheumatoid arthritis is a source of osteoclast differentiation factor. Arthritis Rheum. 2000;43:250–8. Riese RJ, et al. Essential role for cathepsin S in MHC class II-associated invariant chain processing and peptide loading. Immunity. 1996;4:357–66. Riese RJ, et al. Cathepsin S activity regulates antigen presentation and immunity. J Clin Invest. 1998;101:2351–63. Nakagawa TY, et al. Impaired invariant chain degradation and antigen presentation and diminished collagen-induced arthritis in cathepsin S null mice. Immunity. 1999;10:207–17. Biroc SL, et al. Cysteine protease activity is up-regulated in inflamed ankle joints of rats with adjuvant-induced arthritis and decreases with in vivo administration of a vinyl sulfone cysteine protease inhibitor. Arthritis Rheum. 2001;44:703–11. Otto HH, et al. Cysteine proteases and their inhibitors. Chem Rev. 1997;97:133–71. Bromme D, et al. Thiol-dependent cathepsins: pathophysiological implications and recent advances in inhibitor design. Curr Pharm Des. 2002;8:1639–58. Yamashita DS, et al. Cathepsin K and the design of inhibitors of cathepsin K. Curr Pharm Des. 2000;6:1–24. Yasuda Y, et al. The role of cathepsins in osteoporosis and arthritis: rationale for the design of new therapeutics. Adv Drug Deliv Rev. 2005;57:973–93. Lee-Dutra A, et al. Cathepsin S inhibitors: 2004–2010. Expert Opin Ther Pat. 2011;21:311–37. Kumar S, et al. A highly potent inhibitor of cathepsin K (relacatib) reduces biomarkers of bone resorption both in vitro and in an acute model of elevated bone turnover in vivo in monkeys. Bone. 2007;40:122–31. Adami S, et al. Effect of one year treatment with the cathepsin-K inhibitor, balicatib,on bone mineral density (BMD) in postmenopausal women with osteopenia/osteoporosis (abstract). J Bone Miner Res. 2006;21:S24. Runger TM et al. Morphea-like skin reactions in patients treated with the cathepsin K inhibitor balicatib. J Am Acad Dermatol. 2011. Eastell R et al. Safety and efficacy of the Cathepsin K inhibitor, ONO-5334, in postmenopausal osteoporosis—the OCEAN study. J Bone Miner Res. 2011. Gauthier JY, et al. The discovery of odanacatib (MK-0822), a selective inhibitor of cathepsin K. Bioorg Med Chem Lett. 2008;18:923–8. Stoch SA, et al. Effect of the cathepsin K inhibitor odanacatib on bone resorption biomarkers in healthy postmenopausal women: two double-blind, randomized, placebo-controlled phase I studies. Clin Pharmacol Ther. 2009;86:175–82. Bone HG, et al. Odanacatib, a cathepsin-K inhibitor for osteoporosis: a two-year study in postmenopausal women with low bone density. J Bone Miner Res. 2010;25:937–47. Eisman JA, et al. Odanacatib in the treatment of postmenopausal women with low bone mineral density: three-year continued therapy and resolution of effect. J Bone Miner Res. 2011;26:242–51. Bauer DC. Discontinuation of odanacatib and other osteoporosis treatments: here today and gone tomorrow? J Bone Miner Res. 2011;26:239–41. Jensen AB, et al. The cathepsin K inhibitor odanacatib suppresses bone resorption in women with breast cancer and established bone metastases: results of a 4-week, double-blind, randomized, controlled trial. Clin Breast Cancer. 2010;10:452–8.