Table of Contents Author Guidelines Submit a Manuscript
BioMed Research International
Volume 2014, Article ID 309718, 9 pages
http://dx.doi.org/10.1155/2014/309718
Review Article

Cysteine Cathepsin Activity Regulation by Glycosaminoglycans

1Faculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, SI-1000 Ljubljana, Slovenia
2Department of Biochemistry, Molecular and Structural Biology, Jozef Stefan Institute, Jamova Cesta 39, SI-1000 Ljubljana, Slovenia
3Centre of Excellence for Integrated Approaches in Chemistry and Biology of Proteins, Jamova Cesta 39, SI-1000 Ljubljana, Slovenia

Received 16 May 2014; Accepted 2 July 2014; Published 21 December 2014

Academic Editor: George Tzanakakis

Copyright © 2014 Marko Novinec et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. N. D. Rawlings, A. J. Barrett, and A. Bateman, “MEROPS: the database of proteolytic enzymes, their substrates and inhibitors,” Nucleic Acids Research, vol. 40, no. 1, pp. D343–D350, 2012. View at Publisher · View at Google Scholar · View at Scopus
  2. A. Rossi, Q. Deveraux, B. Turk, and A. Sali, “Comprehensive search for cysteine cathepsins in the human genome,” Biological Chemistry, vol. 385, no. 5, pp. 363–372, 2004. View at Publisher · View at Google Scholar · View at Scopus
  3. V. Turk, V. Stoka, O. Vasiljeva et al., “Cysteine cathepsins: from structure, function and regulation to new frontiers,” Biochimica et Biophysica Acta—Proteins and Proteomics, vol. 1824, no. 1, pp. 68–88, 2012. View at Publisher · View at Google Scholar · View at Scopus
  4. M. Novinec and B. Lenarčič, “Papain-like peptidases: Structure, function, and evolution,” Biomolecular Concepts, vol. 4, no. 3, pp. 287–308, 2013. View at Publisher · View at Google Scholar · View at Scopus
  5. O. Vasiljeva, T. Reinheckel, C. Peters, D. Turk, V. Turk, and B. Turk, “Emerging roles of cysteine cathepsins in disease and their potential as drug targets,” Current Pharmaceutical Design, vol. 13, no. 4, pp. 387–403, 2007. View at Publisher · View at Google Scholar · View at Scopus
  6. I. Schechter and A. Berger, “On the size of the active site in proteases. I. Papain,” Biochemical and Biophysical Research Communications, vol. 27, no. 2, pp. 157–162, 1967. View at Publisher · View at Google Scholar · View at Scopus
  7. D. Turk, G. Gunčar, M. Podobnik, and B. Turk, “Revised definition of substrate binding sites of papain-like cysteine proteases,” Biological Chemistry, vol. 379, no. 2, pp. 137–147, 1998. View at Google Scholar · View at Scopus
  8. T. Inaoka, G. Bilbe, O. Ishibashi, K.-I. Tezuka, M. Kumegawa, and T. Kokubo, “Molecular cloning of human cDNA for cathepsin K: novel cysteine proteinase predominantly expressed in bone,” Biochemical and Biophysical Research Communications, vol. 206, no. 1, pp. 89–96, 1995. View at Publisher · View at Google Scholar · View at Scopus
  9. W.-S. Hou, Z. Li, R. E. Gordon et al., “Cathepsin K is a critical protease in synovial fibroblast-mediated collagen degradation,” The American Journal of Pathology, vol. 159, no. 6, pp. 2167–2177, 2001. View at Publisher · View at Google Scholar · View at Scopus
  10. M. Novinec and B. Lenarčic, “Cathepsin K: a unique collagenolytic cysteine peptidase,” Biological Chemistry, vol. 394, no. 9, pp. 1163–1179, 2013. View at Publisher · View at Google Scholar · View at Scopus
  11. T. Zavašnik-Bergant and B. Turk, “Cysteine cathepsins in the immune response,” Tissue Antigens, vol. 67, no. 5, pp. 349–355, 2006. View at Publisher · View at Google Scholar · View at Scopus
  12. D. Brömme, Z. Li, M. Barnes, and E. Mehler, “Human cathepsin V functional expression, tissue distribution, electrostatic surface potential, enzymatic characterization, and chromosomal localization,” Biochemistry, vol. 38, no. 8, pp. 2377–2385, 1999. View at Publisher · View at Google Scholar · View at Scopus
  13. C. Stoeckle, C. Gouttefangeas, M. Hammer, E. Weber, A. Melms, and E. Tolosa, “Cathepsin W expressed exclusively in CD8+ T cells and NK cells, is secreted during target cell killing but is not essential for cytotoxicity in human CTLs,” Experimental Hematology, vol. 37, no. 2, pp. 266–275, 2009. View at Publisher · View at Google Scholar · View at Scopus
  14. A. Almond and J. K. Sheehan, “Glycosaminoglycan conformation: do aqueous molecular dynamics simulations agree with x-ray fiber diffraction?” Glycobiology, vol. 10, no. 3, pp. 329–338, 2000. View at Publisher · View at Google Scholar · View at Scopus
  15. M. Cygler, J. Sivaraman, P. Grochulski, R. Coulombe, A. C. Storer, and J. S. Mort, “Structure of rat procathepsin B: model for inhibition of cysteine protease activity by the proregion,” Structure, vol. 4, no. 4, pp. 405–416, 1996. View at Publisher · View at Google Scholar · View at Scopus
  16. R. Coulombe, P. Grochulski, J. Sivaraman, R. Ménard, J. S. Mort, and M. Cygler, “Structure of human procathepsin L reveals the molecular basis of inhibition by the prosegment,” EMBO Journal, vol. 15, no. 20, pp. 5492–5503, 1996. View at Google Scholar · View at Scopus
  17. J. Sivaraman, M. Lalumière, R. Ménard, and M. Cygler, “Crystal structure of wild-type human procathepsin K,” Protein Science, vol. 8, no. 2, pp. 283–290, 1999. View at Google Scholar · View at Scopus
  18. D. Turk, M. Podobnik, R. Kuhelj, M. Dolinar, and V. Turk, “Crystal structures of human procathepsin B at 3.2 and 3.3 Å resolution reveal an interaction motif between a papain-like cysteine protease and its propeptide,” FEBS Letters, vol. 384, no. 3, pp. 211–214, 1996. View at Publisher · View at Google Scholar · View at Scopus
  19. M. Podobnik, R. Kuhelj, V. Turk, and D. Turk, “Crystal structure of the wild-type human procathepsin B at 2.5 Å resolution reveals the native active site of a papain-like cysteine protease zymogen,” Journal of Molecular Biology, vol. 271, no. 5, pp. 774–788, 1997. View at Publisher · View at Google Scholar · View at Scopus
  20. J. Rozman, J. Stojan, R. Kuhelj, V. Turk, and B. Turk, “Autocatalytic processing of recombinant human procathepsin B is a bimolecular process,” FEBS Letters, vol. 459, no. 3, pp. 358–362, 1999. View at Publisher · View at Google Scholar · View at Scopus
  21. J. Rozman Pungerčar, D. Caglič, M. Sajid et al., “Autocatalytic processing of procathepsin B is triggered by proenzyme activity,” FEBS Journal, vol. 276, no. 3, pp. 660–668, 2009. View at Publisher · View at Google Scholar · View at Scopus
  22. G. Dubin, “Proteinaceous cysteine protease inhibitors,” Cellular and Molecular Life Sciences, vol. 62, no. 6, pp. 653–669, 2005. View at Publisher · View at Google Scholar · View at Scopus
  23. B. Turk, D. Turk, and G. S. Salvesen, “Regulating cysteine protease activity: essential role of protease inhibitors as guardians and regulators,” Current Pharmaceutical Design, vol. 8, no. 18, pp. 1623–1637, 2002. View at Publisher · View at Google Scholar · View at Scopus
  24. B. Turk, V. Turk, and D. Turk, “Structural and functional aspects of papain-like cysteine proteinases and their protein inhibitors,” Biological Chemistry, vol. 378, no. 3-4, pp. 141–150, 1997. View at Google Scholar · View at Scopus
  25. B. Lenarčič and T. Bevec, “Thyropins—new structurally related proteinase inhibitors,” The Biological Chemistry, vol. 379, no. 2, pp. 105–111, 1998. View at Google Scholar · View at Scopus
  26. J. L. Avila and J. Convit, “Inhibition of leucocytic lysosomal enzymes by glycosaminoglycans in vitro,” Biochemical Journal, vol. 152, no. 1, pp. 57–64, 1975. View at Google Scholar · View at Scopus
  27. M. Fonović and B. Turk, “Cysteine cathepsins and extracellular matrix degradation,” Biochimica et Biophysica Acta—General Subjects, vol. 1840, no. 8, pp. 2560–2570, 2014. View at Publisher · View at Google Scholar · View at Scopus
  28. K. Ishidoh and E. Kominami, “Procathepsin L degrades extracellular matrix proteins in the presence of glycosaminoglycans in vitro,” Biochemical and Biophysical Research Communications, vol. 217, no. 2, pp. 624–631, 1995. View at Publisher · View at Google Scholar · View at Scopus
  29. R. W. Mason and S. D. Massey, “Surface activation of pro-cathepsin L,” Biochemical and Biophysical Research Communications, vol. 189, no. 3, pp. 1659–1666, 1992. View at Publisher · View at Google Scholar · View at Scopus
  30. O. Vasiljeva, M. Dolinar, J. Rozman Pungerčar, V. Turk, and B. Turk, “Recombinant human procathepsin S is capable of autocatalytic processing at neutral pH in the presence of glycosaminoglycans,” The FEBS Letters, vol. 579, no. 5, pp. 1285–1290, 2005. View at Publisher · View at Google Scholar · View at Scopus
  31. D. Caglič, J. Rozman Pungerčar, G. Pejler, V. Turk, and B. Turk, “Glycosaminoglycans facilitate procathepsin B activation through disruption of propeptide-mature enzyme interactions,” The Journal of Biological Chemistry, vol. 282, no. 45, pp. 33076–33085, 2007. View at Publisher · View at Google Scholar · View at Scopus
  32. C. Serveau, A. Boulangé, F. Lecaille, F. Gauthier, E. Authié, and G. Lalmanach, “Procongopain from Trypanosoma congolense is processed at basic pH: an unusual feature among cathepsin L-like cysteine proteases,” Biological Chemistry, vol. 384, no. 6, pp. 921–927, 2003. View at Publisher · View at Google Scholar · View at Scopus
  33. J. Sage, F. Mallèvre, F. Barbarin-Costes et al., “Binding of chondroitin 4-sulfate to cathepsin S regulates its enzymatic activity,” Biochemistry, vol. 52, no. 37, pp. 6487–6498, 2013. View at Publisher · View at Google Scholar · View at Scopus
  34. D. Brömme, F. S. Nallaseth, and B. Turk, “Production and activation of recombinant papain-like cysteine proteases,” Methods, vol. 32, no. 2, pp. 199–206, 2004. View at Publisher · View at Google Scholar · View at Scopus
  35. R. Kuhelj, M. Dolinar, J. Rozman Pungerčar, and V. Turk, “The preparation of catalytically active human cathepsin B from its precursor expressed in Escherichia coli in the form of inclusion bodies,” European Journal of Biochemistry, vol. 229, no. 2, pp. 533–539, 1995. View at Publisher · View at Google Scholar · View at Scopus
  36. G. Kopitar, M. Dolinar, B. Štrukelj, J. Pungerčar, and V. Turk, “Folding and activation of human procathepsin S from inclusion bodies produced in Escherichia coli,” European Journal of Biochemistry, vol. 236, no. 2, pp. 558–562, 1996. View at Publisher · View at Google Scholar · View at Scopus
  37. J. Hallgren, D. Spillmann, and G. Pejler, “Structural requirements and mechanism for heparin-induced activation of a recombinant mouse mast cell tryptase, mouse mast cell protease-6: formation of active tryptase monomers in the presence of low molecular weight heparin,” Journal of Biological Chemistry, vol. 276, no. 46, pp. 42774–42781, 2001. View at Publisher · View at Google Scholar · View at Scopus
  38. M. Vanwildemeersch, A.-K. Olsson, E. Gottfridsson, L. Claesson-Welsh, U. Lindahl, and D. Spillmann, “The anti-angiogenic His/Pro-rich fragment of histidine-rich glycoprotein binds to endothelial cell heparan sulfate in a Zn2+-dependent manner,” The Journal of Biological Chemistry, vol. 281, no. 15, pp. 10298–10304, 2006. View at Publisher · View at Google Scholar · View at Scopus
  39. M. Fairhead, S. M. Kelly, and C. F. van der Walle, “A heparin binding motif on the pro-domain of human procathepsin L mediates zymogen destabilization and activation,” Biochemical and Biophysical Research Communications, vol. 366, no. 3, pp. 862–867, 2008. View at Publisher · View at Google Scholar · View at Scopus
  40. P. C. Almeida, I. L. Nantes, C. C. A. Rizzi et al., “Cysteine proteinase activity regulation: a possible role of heparin and heparin-like glycosaminoglycans,” The Journal of Biological Chemistry, vol. 274, no. 43, pp. 30433–30438, 1999. View at Publisher · View at Google Scholar · View at Scopus
  41. Z. Li, W. S. Hou, and D. Brömme, “Collagenolytic activity of cathepsin K is specifically modulated by cartilage-resident chondroitin sulfates,” Biochemistry, vol. 39, no. 3, pp. 529–536, 2000. View at Publisher · View at Google Scholar · View at Scopus
  42. B. D. Gelb, G.-P. Shi, H. A. Chapman, and R. J. Desnick, “Pycnodysostosis, a lysosomal disease caused by cathepsin K deficiency,” Science, vol. 273, no. 5279, pp. 1236–1239, 1996. View at Publisher · View at Google Scholar · View at Scopus
  43. Z. Li, M. Kienetz, M. M. Cherney, M. N. G. James, and D. Brömme, “The crystal and molecular structures of a cathepsin K:chondroitin sulfate complex,” Journal of Molecular Biology, vol. 383, no. 1, pp. 78–91, 2008. View at Publisher · View at Google Scholar · View at Scopus
  44. M. Novinec, L. Kovačič, B. Lenarĉič, and A. Baici, “Conformational flexibility and allosteric regulation of cathepsin K,” Biochemical Journal, vol. 429, no. 2, pp. 379–389, 2010. View at Publisher · View at Google Scholar · View at Scopus
  45. P. Saftig, E. Hunziker, O. Wehmeyer et al., “Impaired osteoclastic bone resorption leads to osteopetrosis in cathepsin-K-deficient mice,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 23, pp. 13453–13458, 1998. View at Publisher · View at Google Scholar · View at Scopus
  46. W. Kafienah, D. Brömme, D. J. Buttle, L. J. Croucher, and A. P. Hollander, “Human cathepsin K cleaves native type I and II collagens at the N-terminal end of the triple helix,” Biochemical Journal, vol. 331, part 3, pp. 727–732, 1998. View at Google Scholar · View at Scopus
  47. P. Garnero, O. Borel, I. Byrjalsen et al., “The collagenolytic activity of cathepsin K is unique among mammalian proteinases,” The Journal of Biological Chemistry, vol. 273, no. 48, pp. 32347–32352, 1998. View at Publisher · View at Google Scholar · View at Scopus
  48. D. Brömme, K. Okamoto, B. B. Wang, and S. Biroc, “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,” Journal of Biological Chemistry, vol. 271, no. 4, pp. 2126–2132, 1996. View at Publisher · View at Google Scholar · View at Scopus
  49. S. Boonen, E. Rosenberg, F. Claessens, D. Vanderschueren, and S. Papapoulos, “Inhibition of cathepsin K for treatment of osteoporosis,” Current Osteoporosis Reports, vol. 10, no. 1, pp. 73–79, 2012. View at Publisher · View at Google Scholar · View at Scopus
  50. W. S. Hou, Z. Li, F. H. Büttner, E. Bartnik, and D. Brömme, “Cleavage site specificity of cathepsin K toward cartilage proteoglycans and protease complex formation,” Biological Chemistry, vol. 384, no. 6, pp. 891–897, 2003. View at Publisher · View at Google Scholar · View at Scopus
  51. V. M. Dejica, J. S. Mort, S. Laverty et al., “Increased type II collagen cleavage by cathepsin K and collagenase activities with aging and osteoarthritis in human articular cartilage,” Arthritis Research and Therapy, vol. 14, no. 3, article R113, 2012. View at Publisher · View at Google Scholar · View at Scopus
  52. V. M. Dejica, J. S. Mort, S. Laverty et al., “Cleavage of type II collagen by cathepsin K in human osteoarthritic cartilage,” The American Journal of Pathology, vol. 173, no. 1, pp. 161–169, 2008. View at Publisher · View at Google Scholar · View at Scopus
  53. Z. Li, Y. Yasuda, W. Li et al., “egulation of collagenase activities of human cathepsins by glycosaminoglycans,” The Journal of Biological Chemistry, vol. 279, no. 7, pp. 5470–5479, 2004. View at Publisher · View at Google Scholar · View at Scopus
  54. Z. Li, W.-S. Hou, C. R. Escalante-Torres, B. D. Gelb, and D. Brömme, “Collagenase activity of cathepsin K depends on complex formation with chondroitin sulfate,” The Journal of Biological Chemistry, vol. 277, no. 32, pp. 28669–28676, 2002. View at Publisher · View at Google Scholar · View at Scopus
  55. O. Borel, E. Gineyts, C. Bertholon, and P. Garnero, “Cathepsin K preferentially solubilizes matured bone matrix,” Calcified Tissue International, vol. 91, no. 1, pp. 32–39, 2012. View at Publisher · View at Google Scholar · View at Scopus
  56. B. Casu, M. Petitou, M. Provasoli, and P. Sinaÿ, “Conformational flexibility: a new concept for explaining binding and biological properties of iduronic acid-containing glycosaminoglycans,” Trends in Biochemical Sciences, vol. 13, no. 6, pp. 221–225, 1988. View at Publisher · View at Google Scholar · View at Scopus
  57. P. C. Almeida, I. L. Nantes, J. R. Chagas et al., “Cathepsin B activity regulation. Heparin-like glycosaminoglycans protect human cathepsin B from alkaline pH-induced inactivation,” Journal of Biological Chemistry, vol. 276, no. 2, pp. 944–951, 2001. View at Publisher · View at Google Scholar · View at Scopus
  58. H. Kirschke, B. Wiederanders, D. Brömme, and A. Rinne, “Cathepsin S from bovine spleen. Purification, distribution, intracellular localization and action on proteins,” Biochemical Journal, vol. 264, no. 2, pp. 467–473, 1989. View at Google Scholar · View at Scopus
  59. T. Y. Nakagawa, W. H. Brissette, P. D. Lira et al., “Impaired invariant chain degradation and antigen presentation and diminished collagen-induced arthritis in cathepsin S null mice,” Immunity, vol. 10, no. 2, pp. 207–217, 1999. View at Publisher · View at Google Scholar · View at Scopus
  60. S. Guo-Ping, J. A. Villadangos, G. Dranoff et al., “Cathepsin S required for normal MHC class II peptide loading and germinal center development,” Immunity, vol. 10, no. 2, pp. 197–206, 1999. View at Publisher · View at Google Scholar · View at Scopus
  61. C. Driessen, R. A. R. Bryant, A. M. Lennon-Duménil et al., “Cathepsin S controls the trafficking and maturation of MHC class II molecules in dendritic cells,” Journal of Cell Biology, vol. 147, no. 4, pp. 775–790, 1999. View at Publisher · View at Google Scholar · View at Scopus
  62. M. Novinec, M. Korenč, A. Caflisch, R. Ranganathan, B. Lenarčič, and A. Baici, “A novel allosteric mechanism in the cysteine peptidase cathepsin K discovered by computational methods,” Nature Communications, vol. 5, Article ID 3287, 2014. View at Publisher · View at Google Scholar
  63. D. Musil, D. Zučič, D. Turk et al., “The refined 2.15 Å X-ray crystal structure of human liver cathepsin B: the structural basis for its specificity,” EMBO Journal, vol. 10, no. 9, pp. 2321–2330, 1991. View at Google Scholar · View at Scopus
  64. M. M. Mohamed and B. F. Sloane, “Cysteine cathepsins: multifunctional enzymes in cancer,” Nature Reviews Cancer, vol. 6, no. 10, pp. 764–775, 2006. View at Publisher · View at Google Scholar · View at Scopus
  65. A. Baici, A. Lang, R. Zwicky, and K. Müntener, “Cathepsin B in osteoarthritis: uncontrolled proteolysis in the wrong place,” Seminars in Arthritis and Rheumatism, vol. 34, no. 2, pp. 24–28, 2004. View at Publisher · View at Google Scholar · View at Scopus
  66. D. Cavallo-Medved, J. Mai, J. Dosescu, M. Sameni, and B. F. Sloane, “Caveolin-1 mediates the expression and localization of cathepsin B, pro-urokinase plasminogen activator and their cell-surface receptors in human colorectal carcinoma cells,” Journal of Cell Science, vol. 118, no. 7, pp. 1493–1503, 2005. View at Publisher · View at Google Scholar · View at Scopus
  67. D. Cavallo-Medved, D. Rudy, G. Blum, M. Bogyo, D. Caglic, and B. F. Sloane, “Live-cell imaging demonstrates extracellular matrix degradation in association with active cathepsin B in caveolae of endothelial cells during tube formation,” Experimental Cell Research, vol. 315, no. 7, pp. 1234–1246, 2009. View at Publisher · View at Google Scholar · View at Scopus
  68. T. T. Lah, M. R. Buck, K. V. Honn et al., “Degradation of laminin by human tumor cathepsin B,” Clinical & Experimental Metastasis, vol. 7, no. 4, pp. 461–468, 1989. View at Publisher · View at Google Scholar · View at Scopus
  69. M. R. Buck, D. G. Karustis, N. A. Day, K. V. Honn, and B. F. Sloane, “Degradation of extracellular-matrix proteins by human cathepsin B from normal and tumour tissues,” Biochemical Journal, vol. 282, no. 1, pp. 273–278, 1992. View at Google Scholar · View at Scopus
  70. V. Hook, T. Toneff, M. Bogyo et al., “Inhibition of cathepsin B reduces beta-amyloid production in regulated secretory vesicles of neuronal chromaffin cells: evidence for cathepsin B as a candidate beta-secretase of Alzheimer's disease,” Biological Chemistry, vol. 386, no. 12, pp. 931–940, 2005. View at Publisher · View at Google Scholar · View at Scopus
  71. C. Wang, B. Sun, Y. Zhou, A. Grubb, and L. Gan, “Cathepsin B degrades amyloid-β in mice expressing wild-type human amyloid precursor protein,” The Journal of Biological Chemistry, vol. 287, no. 47, pp. 39834–39841, 2012. View at Publisher · View at Google Scholar · View at Scopus
  72. B. Sun, Y. Zhou, B. Halabisky et al., “Cystatin C-cathepsin B axis regulates amyloid beta levels and associated neuronal deficits in an animal model of Alzheimer's disease,” Neuron, vol. 60, no. 2, pp. 247–257, 2008. View at Publisher · View at Google Scholar · View at Scopus
  73. M. G. S. Costa, P. R. Batista, C. S. Shida, C. H. Robert, P. M. Bisch, and P. G. Pascutti, “How does heparin prevent the pH inactivation of cathepsin B? Allosteric mechanism elucidated by docking and molecular dynamics,” BMC Genomics, vol. 11, supplement 5, article S5, 2010. View at Publisher · View at Google Scholar · View at Scopus
  74. T. F. R. Costa, F. C. G. D. Reis, and A. P. C. A. Lima, “Substrate inhibition and allosteric regulation by heparan sulfate of Trypanosoma brucei cathepsin L,” Biochimica et Biophysica Acta, vol. 1824, no. 3, pp. 493–501, 2012. View at Publisher · View at Google Scholar · View at Scopus
  75. A. P. Lima, P. C. Almeida, I. L. Tersariol et al., “Heparan sulfate modulates kinin release by Trypanosoma cruzi through the activity of cruzipain,” The Journal of Biological Chemistry, vol. 277, no. 8, pp. 5875–5881, 2002. View at Publisher · View at Google Scholar · View at Scopus
  76. W. A. S. Judice, M. A. Manfredi, G. P. Souza et al., “Heparin modulates the endopeptidase activity of Leishmania mexicana cysteine protease cathepsin L-like rCPB2.8,” PLoS ONE, vol. 8, no. 11, Article ID e80153, 2013. View at Publisher · View at Google Scholar · View at Scopus
  77. J. Y. Gauthier, N. Chauret, W. Cromlish et al., “The discovery of odanacatib (MK-0822), a selective inhibitor of cathepsin K,” Bioorganic and Medicinal Chemistry Letters, vol. 18, no. 3, pp. 923–928, 2008. View at Publisher · View at Google Scholar · View at Scopus
  78. K. Lippuner, “The future of osteoporosis treatment—a research update,” Swiss Medical Weekly, vol. 142, Article ID w13624, 2012. View at Publisher · View at Google Scholar · View at Scopus