Skip to main content

Advertisement

Log in

Assessment of the circulatory concentrations of cathepsin D, cathepsin K, and alpha-1 antitrypsin in patients with knee osteoarthritis

  • Original Article
  • Published:
Irish Journal of Medical Science (1971 -) Aims and scope Submit manuscript

Abstract

Background

Evidence has shown that cysteine protease enzymes, such as cathepsin D, cathepsin A, cathepsin K, and alpha-1 antitrypsin (AAT) are involved in the chronic degenerative joint process. This study aimed to determine the potential involvement of cathepsin K, cathepsin D, and AAT in patients with osteoarthritis (OA).

Methods

This study was performed on 31 patients with knee OA and 29 age- and sex-matched healthy subjects (both with Fars ethnicity from Iran). American College of Rheumatology (ACR) criteria were used to diagnose OA patients. The clinical status of the patients was scored by Western Ontario McMaster Universities Osteoarthritis (WOMAC), and pain intensity was measured by the Visual Analog Scale (VAS). The serum level of AAT was measured using high-resolution cellulose acetate electrophoresis. Additionally, serum levels of cathepsin D and cathepsin K were measured by enzyme-linked immunosorbent assay (ELISA).

Results

The findings showed that the serum level of cathepsin K was significantly increased in OA patients compared to healthy subjects (P = 0.01), while there was no significant difference between serum level of cathepsin D in study groups (P = 0.2). In addition, the serum concentration of AAT was significantly decreased in OA patients compared to healthy subjects (P = 0.003). There was a significant correlation between WOMAC score and age (r = 0.644, P = 0.0001) and VAS (r = 0.866, P < 0.0001) in OA patients.

Conclusions

The decreased level of AAT in OA patients and a rise in serum level of cathepsin K are involved in the pathogenesis of OA via stimulation of bone resorption and cartilage degradation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

Availability of data and material

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Code availability

The software codes used in this study are available from the corresponding author on reasonable request.

References

  1. Grandi FC, Bhutani N (2020) Epigenetic therapies for osteoarthritis. Trends Pharmacolog Sci

  2. Chu L, Liu X, He Z et al (2020) Articular cartilage degradation and aberrant subchondral bone remodeling in patients with osteoarthritis and osteoporosis. J Bone Miner Res 35(3):505–515

    Article  CAS  PubMed  Google Scholar 

  3. He Y, Li Z, Alexander PG et al (2020) Pathogenesis of osteoarthritis: risk factors, regulatory pathways in chondrocytes, and experimental models. Biology 9(8):194

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Fathollahi A, Aslani S, Jamshidi A, Mahmoudi M (2019) Epigenetics in osteoarthritis: novel spotlight. J Cell Physiol 234(8):12309–12324

    Article  CAS  PubMed  Google Scholar 

  5. Ahmadi M, Gharibi T, Dolati S et al (2017) Epigenetic modifications and epigenetic based medication implementations of autoimmune diseases. Biomed Pharmacother 87:596–608

    Article  CAS  PubMed  Google Scholar 

  6. Kalaitzoglou E, Griffin TM, Humphrey MB et al (2017) Innate immune responses and osteoarthritis. Curr Rheumatol Rep 19(8):45

    Article  PubMed  Google Scholar 

  7. Ben-Aderet L, Merquiol E, Fahham D et al (2015) Detecting cathepsin activity in human osteoarthritis via activity-based probes. Arthritis Res Ther 17(1):69–69. https://doi.org/10.1186/s13075-015-0586-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Vinardell T, Dejica V, Poole A et al (2009) Evidence to suggest that cathepsin K degrades articular cartilage in naturally occurring equine osteoarthritis. Osteoarthr Cartil 17(3):375–383

    Article  CAS  PubMed  Google Scholar 

  9. Lindström E, Rizoska B, Tunblad K et al (2018) The selective cathepsin K inhibitor MIV-711 attenuates joint pathology in experimental animal models of osteoarthritis. J Transl Med 16(1):56

    Article  PubMed  PubMed Central  Google Scholar 

  10. Martel-Pelletier J, Wildi LM, Pelletier JP (2012) Future therapeutics for osteoarthritis. Bone 51(2):297–311

    Article  CAS  PubMed  Google Scholar 

  11. Olszewska-Slonina D, Matewski D, Jung S et al (2013) The activity of cathepsin D and alpha-1 antitrypsin in hip and knee osteoarthritis. Acta Biochim Pol 60(1)

  12. Olszewska D, Drewa T, Makarewicz R et al (2001) Significance of cathepsin B and D in physiologic and pathologic processes. Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego 10(55):65–70

    CAS  PubMed  Google Scholar 

  13. Xia H, Huang J, Mao F et al (2014) Activity of cathepsin D and alpha-1 antitrypsin in patients with hip or knee osteoarthritis Zhong nan da xue xue bao Yi xue ban. J Cent South Univ (Med Sci) 39(11):1151–1156

    CAS  PubMed  Google Scholar 

  14. Olszewska-Slonina D, Jung S, Matewski D et al (2015) Lysosomal enzymes in serum and synovial fluid in patients with osteoarthritis. Scand J Clin Lab Invest 75(2):145–151

    Article  CAS  PubMed  Google Scholar 

  15. Karnaukhova E, Ophir Y, Golding B (2006) Recombinant human alpha-1 proteinase inhibitor: towards therapeutic use. Amino Acids 30(4):317–332

    Article  CAS  PubMed  Google Scholar 

  16. Song S (2018) Alpha-1 antitrypsin therapy for autoimmune disorders chronic obstructive pulmonary diseases. Journal of the COPD Foundation 5(4):289

    Article  PubMed  PubMed Central  Google Scholar 

  17. Kozawa E, Cheng XW, Urakawa H et al (2016) Increased expression and activation of cathepsin K in human osteoarthritic cartilage and synovial tissues. J Orthop Res 34(1):127–134

    Article  CAS  PubMed  Google Scholar 

  18. Hayami T, Zhuo Y, Wesolowski GA et al (2012) Inhibition of cathepsin K reduces cartilage degeneration in the anterior cruciate ligament transection rabbit and murine models of osteoarthritis. Bone 50(6):1250–1259. https://doi.org/10.1016/j.bone.2012.03.025

    Article  CAS  PubMed  Google Scholar 

  19. Conaghan PG, Bowes MA, Kingsbury SR et al (2020) Disease-modifying effects of a novel cathepsin K inhibitor in osteoarthritis: a randomized controlled trial. Ann Intern Med 172(2):86–95

    Article  PubMed  Google Scholar 

  20. Nwosu LN, Gowler PR, Burston JJ et al (2018) Analgesic effects of the cathepsin K inhibitor L-006235 in the monosodium iodoacetate model of osteoarthritis pain. Pain reports 3(6)

  21. Olszewska-Slonina D, Matewski D, Jung S et al (2013) The activity of cathepsin D and alpha-1 antitrypsin in hip and knee osteoarthritis. Acta Biochim Pol 60(1):99–106

    Article  CAS  PubMed  Google Scholar 

  22. Hutchison D (1973) Alpha-1-antitrypsin deficiency and pulmonary emphysema: the role of proteolytic enzymes and their inhibitors. Br J Dis Chest 67(3):171–196

    Article  CAS  PubMed  Google Scholar 

  23. Laurell CB, Eriksson S (1963) The electrophoretic α; 1-globulin pattern of serum in α; 1-antitrypsin deficiency. Scand J Clin Lab Invest 15(2):132–140

    Article  CAS  Google Scholar 

  24. Janciauskiene S, Wrenger S, Immenschuh S et al (2018) The multifaceted effects of alpha1-antitrypsin on neutrophil functions. Front Pharmacol 9:341

    Article  PubMed  PubMed Central  Google Scholar 

  25. Wang S, Zhou J, Wei X et al (2015) Identification of α1-antitrypsin as a potential candidate for internal control for human synovial fluid in Western blot. Rheumatology (Sunnyvale, Calif):006

  26. Awbrey B, Kuong S, MacNeil K, Wright M (1993) The role of alpha-1-protease inhibitor (A1PI) in the inhibition of protease activity in human knee osteoarthritis. Agents Actions Suppl 39:167–171

    CAS  PubMed  Google Scholar 

  27. Janciauskiene S, Welte T (2016) Well-known and less well-known functions of alpha-1 antitrypsin. Its role in chronic obstructive pulmonary disease and other disease developments. Ann Am Thoracic Soc 13(Supplement 4):S280-S288

  28. Wanner A (2020) Towards new therapeutic solutions for alpha-1 antitrypsin deficiency: role of the alpha-1 foundation

  29. Tüzün EH, Eker L, Aytar A et al (2005) Acceptability, reliability, validity and responsiveness of the Turkish version of WOMAC osteoarthritis index. Osteoarthritis Cartilage 13(1):28–33

    Article  PubMed  Google Scholar 

  30. Fathi HM (2019) Unilateral versus bilateral primary knee osteoarthritis: relation to the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC), C-reactive protein and radiological assessment in Egyptian patients. Egypt Rheumatolog 41(4):271–276

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Contributions

All authors read and approved the final manuscript. Conception and design: MA and AKH. Development of methodology: MA. Acquisition of data (patient interviews, treatment data, and assessments of oncologists): MR, MF. Analysis and interpretation of data: MR. Writing, review, and/or revision of the manuscript: MA. Administrative, technical, or material support: AKH.

Corresponding author

Correspondence to Mitra Abbasifard.

Ethics declarations

Ethics approval and consent to participate

This study was approved by the ethics committee of Rafsanjan University of Medical Sciences. Written informed consent was obtained from all participants. All procedures performed in this study were in accordance with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Khoshdel, A., Forootan, M., Afsharinasab, M. et al. Assessment of the circulatory concentrations of cathepsin D, cathepsin K, and alpha-1 antitrypsin in patients with knee osteoarthritis. Ir J Med Sci 192, 1191–1196 (2023). https://doi.org/10.1007/s11845-022-03061-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11845-022-03061-3

Keywords

Navigation