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Abstract

The aim of the study was to identify effective biomarkers of changes in bone mineral density (BMD) at different stages of rheumatoid arthritis patients from South Indian population, using disease activity score in 28 joints (DAS28) which is being used as a measurement for assessing disease activity in patients with rheumatoid arthritis. The study was carried out in 92 rheumatoid arthritis patients. Serum level of tartrateresistant acid phosphatase-5b (TRAP-5b) and cathepsin K was measured using ELISA. Serum rheumatoid factor (RF) and C-reactive protein (CRP) was recorded by the attending rheumatologists. The C-reactive protein (CRP) was quantified using a latex immunoturbidimetric method. The rheumatoid arthritis (RA) was measured by turbidimetric immunoassay method. The bone mineral density (BMD) T-score was calculated according to WHO guidelines. Reverse transcription PCR (RT-PCR) was used to determine the expression of cathepsin K. The rheumatoid arthritis (RA) patients were categorized into three groups based on the DAS28 score as inactive (DAS ≤ 3.2), moderately active (DAS > 3.2 ≤ 5.1) and very active (DAS > 5.1) at the time of admission. Out of 92 patients, 16 (17.4%) patients had inactive disease condition, 42 (45.6%) patients had moderately active disease condition and 34 (37%) patients had very active disease condition. The mean BMD was significantly lower in very active (0.28 ± 0.04; p < 0.001) as compared with moderately active (0.71 ± 0.13; p < 0.001) and inactive (1.21 ± 0.14). TRAP5b and cathepsin K showed significant increases in very active group (p < 0.001) as compared with moderately active (p < 0.001) and inactive groups. In conclusion, The biomarker TRAP-5b and cathepsin K identified in this study may become a new and highly specific biomarker for rheumatoid arthritis 

Keywords

Rheumatoid arthritis Cathepsin K TRAP5b Osteoclast Bone mineral density

Article Details

How to Cite
Thangavel, S., Krishnamoorthy, E., Jaganathan, S. S., Padmanaban, A. M., & Samuel, S. (2023). Association of Cathepsin K and Tartrate- Resistant Acid Phosphatase-5b in Different Stages of Rheumatoid Arthritis Patients in South Indian Population. Asian Journal of Organic & Medicinal Chemistry, 8(1), 1–6. https://doi.org/10.14233/ajomc.2023.AJOMC-P27954

References

  1. E.D. Harris and G.S. Firestein, eds.: G.S. Firestein, R.C. Budd, E.D. Harris, I.B. McInnes, S. Ruddy and J.S. Sergent, Clinical Features of Rheumatoid Arthritis, In: Kelley’s Text Book of Rheumatology, Saunders Elsevier: Philadelphia, edn. 8, p. 1087 (2009).
  2. D.L. Scott, C. Smith and G. Kingsley, What are the Consequences of Early Rheumatoid Arthritis for the Individual? Best Pract. Res. Clin. Rheumatol., 19, 117 (2005); https://doi.org/10.1016/j.berh.2004.08.007
  3. A.N. Malaviya, S.K. Kapoor, R.R. Singh, A. Kumar and I. Pande, Prevalence of Rheumatoid Arthritis in the Adult Indian Population, Rheumatol. Int., 13, 131 (1993); https://doi.org/10.1007/BF00301258
  4. G.S. Firestein, eds.: W.N. Kelley, E.D. Harris, S. Ruddy and C.B. Sledge, Etiology and Pathogenesis of Rheumatoid Arthritis. In: Textbook of Rheumatology, WB Saunders: Philadelphia, edn. 5, pp. 851-897 (1997).
  5. G.S. Firestein, Invasive Fibroblast-like Synoviocytes in Rheumatoid Arthritis. Passive Responders or Transformed Aggressors? Arthritis Rheum., 39, 1781 (1996); https://doi.org/10.1002/art.1780391103
  6. M. Tsuji, K. Hirakawa, A. Kato and K. Fujii, The Possible Role of C-fos Expression in Rheumatoid Cartilage Destruction, J. Rheumatol., 27, 1606 (2000).
  7. M. Bromley and D.E. Woolley, Chondroclasts and Osteoclasts at Subchondral Sites of Erosion in the Rheumatoid Joint, Arthritis Rheum., 27, 968 (1984); https://doi.org/10.1002/art.1780270902
  8. E.M. Gravallese, Y. Harada, J.T. Wang, A.H. Gorn, T.S. Thornhill and S.R. Goldring, Identification of Cell Types Responsible for Bone Resorption in Rheumatoid Arthritis and Juvenile Rheumatoid Arthritis, Am. J. Pathol., 152, 943 (1998).
  9. H. Nagase and Y. Okada, eds.: W.N. Kelley, E.D. Harris, S. Ruddy and C.B. Sledge, Proteinases and Matrix Degradation, In: Textbook of Rheumatology, WB Saunders: Philadelphia, edn. 5, pp. 323-341 (1997).
  10. D. Bromme, Cysteine Proteases as Therapeutic Targets, Drug News Perspect., 12, 73 (1999); https://doi.org/10.1358/dnp.1999.12.2.661337
  11. T.E. Cawston, Metalloproteinase Inhibitors and the Prevention of Connective Tissue Breakdown, Pharmacol. Ther., 70, 163 (1996); https://doi.org/10.1016/0163-7258(96)00015-0
  12. H.A. Chapman, R.J. Riese and G.P. Shi, Emerging Roles for Cysteine Proteases in Human Biology, Annu. Rev. Physiol., 59, 63 (1997); https://doi.org/10.1146/annurev.physiol.59.1.63
  13. D.S. Yamashita and R.A. Dodds, Cathepsin K and the Design of hnhibitors of Cathepsin K, Curr. Pharm. Des., 6, 1 (2000); https://doi.org/10.2174/1381612003401569
  14. S. Vasikaran, R. Eastell, O. Bruyère, A.J. Foldes, A. Griesmacher, P. arnero, M. McClung, H.A. Morris, S. Silverman, T. Trenti, D.A. Wahl, C. Cooper and J.A. Kanis, Markers of Bone Turnover for the Prediction f Fracture Risk and Monitoring of Osteoporosis Treatment: a Need for International Reference Standards, Osteoporos. Int., 22, 391 (2011); https://doi.org/10.1007/s00198-010-1501-1
  15. J. Al-Bishri, S.M. Attar, N. Bassuni, Y. Al-Nofaiey, H. Qutbuddeen, S. Al-Harthi and S. Subahi, Clin. Med: Arthritis Musculoskeletal Disord., 6, 11 (2013); https://doi.org/10.4137/CMAMD.S11481
  16. I. Bajraktari, T. Backa Cico, V. Sahatciu Meka, H. Bajraktari, V. Saiti, B. Krasniqi and F. Muslimi, Demographic Features of Patients with Rheumatoid Arthritis in Kosovo, Med. Arh., 68, 407 (2014); https://doi.org/10.5455/medarh.2014.68.407-410
  17. A. Bal, S. Ataman, H. Bodur, A. Rezvani, N. Paker, N. Tastekin, A.g. Karatepe, P. Borman, M. Yener, K. Nas, M. Sezgin, P. Yazgan, I. Tekeoglu, B. Dogu, Z. Altay, M. Kirnap, A. Gürgan, A. Gür, S. Hizmetli, Z. Günendi, R. Erdem, H. Ugurlu, E. Inal, N. Ölmez, E. Kozanoglu, Ö. Öken, S. Özel, Ü. Dündar, A. Akinci, C. Öztürk, K. Sivrioglu, M.t. Duruöz, E. Aydog E. Çapkin, L. Altan, D. Evcik, O. Durmus, I. Yagci, Ö.F. Sendur, F.M. Sertpoyraz, A. Özgül, K. Senel and K. Çapaci, Characteristics of Patients With Rheumatoid Arthritis in Turkey: Results From the Turkish League Against Rheumatism Rheumatoid Arthritis Registry, Arch. Rheumatol., 30, 16 (2015); https://doi.org/10.5606/ArchRheumatol.2015.4224
  18. B.O. Owino, G.O. Oyoo and C.F. Otieno, Socio-Demographic and Clinical Aspects of Rheumatoid Arthritis, East Afr. Med. J., 86, 204 (2009); https://doi.org/10.4314/eamj.v86i5.54190 Asian Journal of Organic & Medicinal Chemistry 5
  19. E. Inoue, H. Yamanaka, M. Hara, T. Tomatsu and N. Kamatani, Comparison of Disease Activity Score (DAS)28- Erythrocyte Sedimentation Rate and DAS28-C-Reactive Protein Threshold Values, Ann. Rheum. Dis., 66, 407 (2007); https://doi.org/10.1136/ard.2006.054205
  20. T.K. Kvien, M.S. Heiberg, E. Lie, C. Kaufmann, K. Mikkelsen, B.Y. Nordvag and E. Rødevand, A Norwegian DMARD Register: Prescriptions of Dmards and Biological Agents to Patients with Inflammatory Rheumatic Diseases, Clin. Exp. Rheumatol., 23(Suppl 39), 188 (2005).
  21. G. Lapadula, G. Ferraccioli, C. Ferri, L. Punzi and F. Trotta, GISEA: an Italian Biological Agents Registry in Rheumatology, Reumatismo, 63, 155 (2011); https://doi.org/10.4081/reumatismo.2011.155
  22. T. Sokka, Increases in use of Methotrexate Since the 1980s, Clin. Exp. Rheumatol., 28(Suppl 61), S13 (2010)
  23. B.D. Gelb, G.P. Shi, H.A. Chapman and R.J. Desnick, Pycnodysostosis, a Lysosomal Disease Caused by Cathepsin K Deficiency, Science, 273, 1236 (1996); https://doi.org/10.1126/science.273.5279.1236
  24. Z. Li, W.S. Hou and D. Bromme, Collagenolytic Activity of Cathepsin K Is Specifically Modulated by Cartilage-Resident Chondroitin Sulfates, Biochemistry, 39, 529 (2000); https://doi.org/10.1021/bi992251u
  25. R.A. Dodds, J.R. Connor, F.H. Drake and M. Gowen, Expression of Cathepsin K Messenger RNA in Giant Cells and their Precursors in Human Osteoarthritic Synovial Tissues, Arthritis Rheum., 42, 1588 (1999); https://doi.org/10.1002/1529 0131(199908)42:8<1588::AIDANR4> 3.0.CO;2-S
  26. G. Huet, R.M. Flipo, C. Colin, A. Janin, M. Collyn-d’Hooghe, B. Hemon, R. Lafyatis, B. Duquesnoy and P. Degand, Stimulation of the Secretion of Latent Cysteine Proteinase Activity by Tumor Necrosis Factor A and Interleukin-1, Arthritis Rheum., 36, 772 (1993); https://doi.org/10.1002/art.1780360606
  27. R. Lemaire, G. Huet, F. Zerimech, G. Grard, C. Fontaine, B. Duquesnoy and R.M. Flipo, Selective Induction of the Secretion of Cathepsins B and L by Cytokines in Synovial Fibroblast-like Cells, Rheumatology,
  28. , 735 (1997); https://doi.org/10.1093/rheumatology/36.7.735 28. L. Svelander, H. Erlandsson-Harris, L. Astner, U. Grabowska, L. Klareskog, E. Lindstrom and E. Hewitt, Inhibition of Cathepsin K Reduces Bone Erosion, Cartilage Degradation and Inflammation Evoked by Collageninduced Arthritis in Mice, Eur. J. Pharmacol., 613, 155 (2009); https://doi.org/10.1016/j.ejphar.2009.03.074
  29. M. Skoumal, G. Kolarz, G. Haberhauer, W. Woloszczuk, G. Hawa and A. Klingler, Osteoprotegerin and the Receptor Activator of NF kappa B Ligand in the Serum and Synovial Fluid. A Comparison of Patients with Longstanding Rheumatoid Arthritis and Osteoarthritis, Rheumatol. Int., 26, 63 (2005); https://doi.org/10.1007/s00296-004-0579-1
  30. T. Tomizawa, H. Ito, K. Murata, M. Hashimoto, M. Tanaka, K. Murakami, K. Nishitani, M. Azukizawa, A. Okahata, K. Doi, M. Saito, M. Furu, M. Hamaguchi, T. Mimori and S. Matsuda, Distinct Biomarkers for Different Bones in Osteoporosis with Rheumatoid Arthritis, Arthritis Res. Ther., 21, 174 (2019); https://doi.org/10.1186/s13075-019-1956-1
  31. P. Gradin, K. Hollberg, A.I. Cassady, P. Lång and G. Andersson, Transgenic Overexpression of Tartrate-Resistant Acid Phosphatase is Associated with Induction of Osteoblast Gene Expression and Increased Cortical Bone Mineral Content and Density, Cells Tissues Organs, 196, 68 (2012); https://doi.org/10.1159/000330806
  32. S. Mose, C. Menzel, A.A. Kurth, K. Obert, I. Breidert, K. Borowsky and H.D. Böttcher, Tartrate-Resistant Acid Phosphatase 5b as Serum Marker of Bone Metabolism in Cancer Patients, Anticancer Res., 23, 2783 (2003).
  33. P. Gerdhem, K.K. Ivaska, S.L. Alatalo, J.M. Halleen, J. Hellman, A. Isaksson, K. Pettersson, H.K. Väänänen, K. Akesson and K.J. Obrant
  34. Biochemical Markers of Bone Metabolism and Prediction of Fracture in Elderly Women, J. Bone Miner. Res., 19, 386 (2004); https://doi.org/10.1359/JBMR.0301244
  35. S.-H. Tsai, C.-Y. Chen, C.-H. Ku, A.J. Janckila, L.T. Yam, J.-C. Yu, K.W. Chuang and T.Y. Chao, The Semiquantitative Bone Scintigraphy Index Correlates With Serum Tartrate-Resistant Acid Phosphatase Activity in Breast Cancer Patients With Bone Metastasis, Mayo Clin. Proc., 82, 917 (2007); https://doi.org/10.4065/82.8.917
  36. S.L. Alatalo, K.K. Ivaska, S.G. Waguespack, M.J. Econs, H.K. Väänänen and J.M. Halleen, Osteoclast-Derived Serum Tartrate-Resistant Acid Phosphatase 5b in Albers-Schonberg Disease (Type II Autosomal Dominant Osteopetrosis), Clin. Chem., 50, 883 (2004); https://doi.org/10.1373/clinchem.2003.029355
  37. A.J. Janckila, D.H. Neustadt and L.T. Yam, Significance of Serum TRACP in Rheumatoid Arthritis, J. Bone Miner. Res., 23, 1287 (2008); https://doi.org/10.1359/jbmr.080329
  38. A. Nenonen, S. Cheng, K.K. Ivaska, S.L. Alatalo, T. Lehtimaki, H. Schmidt Gayk, K. UusiRasi, A. Heinonen, P. Kannus, H. Sievanen, I. Vuori, H.K. Vaananen and J.M. Halleen, Serum TRACP 5b is a Useful Marker for Monitoring Alendronate Treatment: Comparison with Other Markers of Bone Turnover, J. Bone Miner. Res., 20, 1804 (2005); https://doi.org/10.1359/JBMR.050403
  39. T. Cheng, M. Wang, Z. Chen, R.A. Eisenberg, Y. Zhang, Y. Zou, Y. Deng, M. Wang and L. Zhou, Tartrate-Resistant Acid Phosphatase 5b is a Potential Biomarker for Rheumatoid Arthritis: A Pilot Study in Han Chinese, Chin. Med. J., 127, 2894 (2014); https://doi.org/10.3760/cma.j.issn.0366-6999.20140670 6 Thangavel et al.