Association of inflammatory, genetic, and epigenetic markers with Kellgren-Lawrence grading in post-traumatic osteoarthritis of knee: A protocol

doi:10.5493/wjem.v15.i4.107843

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World Journal of Experimental Medicine

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2220-315x

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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World J Exp Med. Dec 20, 2025; 15(4): 107843
Published online Dec 20, 2025. doi: 10.5493/wjem.v15.i4.107843

Association of inflammatory, genetic, and epigenetic markers with Kellgren-Lawrence grading in post-traumatic osteoarthritis of knee: A protocol

Keerthy Rethinam Meenakshi Sundaram, Thiagarajan Keddin Alwar, Ramchand Nannapan, Vinodhini Vellore Mohanakrishnan, Santhi Silambanan

Keerthy Rethinam Meenakshi Sundaram, Santhi Silambanan, Department of Biochemistry, Sri Ramachandra Institute of Higher Education and Research, Chennai 600116, Tamil Nādu, India

Thiagarajan Keddin Alwar, Department of Arthroscopy and Sports Medicine, Sri Ramachandra Institute of Higher Education and Research, Chennai 600116, Tamil Nādu, India

Ramchand Nannapan, Saksin Lifesciences Pvt Ltd, Chennai 600113, Tamil Nādu, India

Vinodhini Vellore Mohanakrishnan, Department of Biochemistry, SRM Medical College Hospital and Research Centre, Chennai 603203, Tamil Nādu, India

Author contributions: Sundaram KRM, Alwar TK, Nanappan R, Mohanakrishnan VV and Silambanan S designed the research study; Sundaram KRM, Alwar TK, Nanappan R and Silambanan S performed the research; Sundaram KRM, and Silambanan S contributed new reagents and analytic tools; Sundaram KRM, Alwar TK, Nanappan R, Mohanakrishnan VV and Silambanan S analyzed the data and wrote the manuscript; All authors have read and approved the final manuscript.

Supported by ICMR, No. U04M200059.

Institutional review board statement: The study is approved by the Institutional Ethics Committee of Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai (CSP-MED/21/JAN/65/03, dated 11.02.2021).

Clinical trial registration statement: The study is registered with Indian Council of Medical Research, India, CTRI/2025/03/083060 (https://ctri.nic.in/Clinicaltrials/Login.php).

Informed consent statement: Written informed consent is obtained.

Conflict-of-interest statement: All authors declare that there were no conflicts of interest.

CONSORT 2010 statement: The authors have read the CONSORT 2010 statement, and the manuscript was prepared and revised according to the CONSORT 2010 statement.

Data sharing statement: All the required data are provided in the article itself.

Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/

Corresponding author: Santhi Silambanan, MD, Professor, Department of Biochemistry, Sri Ramachandra Institute of Higher Education and Research, Chennai 600116, Tamil Nādu, India. santhisilambanan@sriramachandra.edu.in

Received: April 2, 2025
Revised: May 14, 2025
Accepted: August 14, 2025
Published online: December 20, 2025
Processing time: 265 Days and 5.2 Hours

Abstract

BACKGROUND

Post-traumatic osteoarthritis (PTOA) occurs due to cartilage degeneration caused by injuries like bone fractures, ligament tears, and soft tissue injuries in and around the joint. It is diagnosed by X-ray in the later stages. Early diagnosis may be possible by analyzing biochemical and molecular markers, facilitating early management.

AIM

To characterize inflammatory, genetic, and epigenetic markers that aid in the diagnosis and prognosis of knee PTOA.

METHODS

The prospective cohort study is conducted at a tertiary care hospital, India. The study includes 140 participants: 70 (controls), and 70 (cases) sustained trauma to knee. Written informed consent is obtained. Serum interleukin (IL)-6, IL-1β, IL-10, cartilage oligomeric matrix protein, transforming growth factor-β1, matrix metalloproteinase-13, and oxidized-LDL and urine C-terminal cross-linked telopeptides of type II collagen are analyzed by ELISA. Genetic and epigenetic studies are done. Ethics approval is obtained. Statistical analysis by SPSS software version 16.

RESULTS

Biomarkers will be correlated with the X-ray grading as per the Kellgren-Lawrence scale.

CONCLUSION

These mediators can be potential markers to assess the disease burden, prognosis, and severity. They may also help as therapeutic targets to customize personalized therapy.

Keywords: Biomarkers; Cytokines; Inflammation; Knee joint; Osteoarthritis

Core Tip: Post-traumatic osteoarthritis (PTOA) is a secondary osteoarthritis that follows a joint injury. The knee is the most frequently affected joint, and the extent of injury ranges from simple to complex. PTOA is characterized by joint pain, swelling, and restricted movement. It is diagnosed beyond stage 2 of the Kellgren-Lawrence grading system, as evidenced by an X-ray. The disease begins after the joint injury, which further progresses due to complex biochemical interactions of cytokines, oxidative stress markers, enzymes, and collagen breakdown products. These markers can help us in a multidisciplinary approach thus emphasizing early intervention, biomarker-guided therapies, and mechanical stabilization thus, improving patient outcomes.