Altered Osteoprotegerin/RANKL Ratio Contributes to Primary Liver Dysfunction and Bone Loss in Rheumatoid Arthritis: Insights into Extra-Articular Manifestations

Authors

  • Shukdeb Acharjee Department of Molecular Biology and Bioinformatics, Tripura University (A Central University)
  • Manash Das Department of Medical Laboratory Technology, Women’s Polytechnic, Hapania, Tripura,
  • Subankar Deb 1Department of Molecular Biology & Bioinformatics, Tripura University, Suryamaninagar, Tripura, 799022, India
  • Avik Sarkar Department of Clinical Immunology & Rheumatology, IPGME&R, SSKM Hospital, Kolkata, 700020, India
  • Chinmoy Ghosh Department of Oral and Craniofacial Molecular Biology, Philips Institute for Oral Health Research, School of Dentistry, Virginia Commonwealth University, Richmond, VA, 23298, USA
  • Surajit Bhattacharjee a:1:{s:5:"en_US";s:100:"Associate Professor and HOD, Department of Molecular Biology and Bioinformatics, Tripura University ";}

DOI:

https://doi.org/10.55184/ijpas.v76i04.286

Abstract

Background: Rheumatoid arthritis (RA) is an autoimmune disease characterized by sustained systemic inflammation, leading to joint damage and extra-articular manifestations, such as liver dysfunction. Hypothesis: Reduced osteoprotegerin (OPG) and increased receptor activator of nuclear factor-kappa B ligand (RANKL) levels in RA contribute to primary liver dysfunction. Materials and Methods: A total of 284 female RA patients and 78 healthy controls were included. RA patients were categorized into low (LDA), moderate (MDA), and high disease activity (HDA) groups based on disease activity scores (DAS-28). Serum levels of interleukin-18 (IL-18), tumor necrosis factor-alpha (TNF-α), OPG, and RANKL were measured through ELISA. Liver function tests, bone mineral density (BMD), and histological analyses were performed. Results: Serum IL-18, TNF-α, and RANKL levels were significantly elevated, while OPG levels were reduced in RA patients, with the highest alterations observed in the HDA group. The OPG/RANKL ratio was inversely correlated with disease activity, liver enzyme levels, and positively correlated with BMD. Histological analysis revealed synovial inflammation and pannus formation, with increased expression of IL-18, TNF-α, and RANKL. RA patients exhibited abnormal liver function parameters, decreased BMD, and osteopenia/osteoporosis. Conclusion: Sustained inflammation in RA, characterized by altered OPG/RANKL homeostasis, contributes to primary liver dysfunction and bone loss, suggesting a potential therapeutic target for managing extra-articular manifestations.

Author Biographies

Shukdeb Acharjee, Department of Molecular Biology and Bioinformatics, Tripura University (A Central University)

Research Scholar

Manash Das, Department of Medical Laboratory Technology, Women’s Polytechnic, Hapania, Tripura,

Associate Professor, Department of Medical Laboratory Technology, Women’s Polytechnic, Hapania, Tripura, 799130, India

Subankar Deb, 1Department of Molecular Biology & Bioinformatics, Tripura University, Suryamaninagar, Tripura, 799022, India

Department of Molecular Biology & Bioinformatics, Tripura University, Suryamaninagar, Tripura, 799022, India

Avik Sarkar, Department of Clinical Immunology & Rheumatology, IPGME&R, SSKM Hospital, Kolkata, 700020, India

Postdoc, Department of Clinical Immunology & Rheumatology, IPGME&R, SSKM Hospital, Kolkata, 700020, India

Chinmoy Ghosh, Department of Oral and Craniofacial Molecular Biology, Philips Institute for Oral Health Research, School of Dentistry, Virginia Commonwealth University, Richmond, VA, 23298, USA

Department of Oral and Craniofacial Molecular Biology, Philips Institute for Oral Health Research, School of Dentistry, Virginia Commonwealth University, Richmond, VA, 23298, USA

Published

24-12-2024

How to Cite

Acharjee, S., Das, M., Deb, S., Sarkar, A., Ghosh, C., & Bhattacharjee, S. (2024). Altered Osteoprotegerin/RANKL Ratio Contributes to Primary Liver Dysfunction and Bone Loss in Rheumatoid Arthritis: Insights into Extra-Articular Manifestations. INDIAN JOURNAL OF PHYSIOLOGY AND ALLIED SCIENCES, 76(04). https://doi.org/10.55184/ijpas.v76i04.286