Distinct patterns of cytokines, chemokines, and growth factors in synovial fluid after ACL injury in comparison to osteoarthritis

Author:

Rai Muhammad Farooq123ORCID,Cai Lei4,Chinzei Nobuaki4,Schmidt Eric J.5,Yousuf Omer4ORCID,Guilak Farshid4678ORCID,Brophy Robert H.4ORCID

Affiliation:

1. Department of Biological Sciences College of Medicine and Health Sciences, Khalifa University Abu Dhabi United Arab Emirates

2. Division of Rheumatology, Department of Medicine Washington University School of Medicine St. Louis Missouri USA

3. Department of Biomedical Engineering Saint Louis University of Science and Engineering St. Louis Missouri USA

4. Department of Orthopedic Surgery Washington University School of Medicine St. Louis Missouri USA

5. Department of PA Medicine, College of Medical Science University of Lynchburg Lynchburg Verginia USA

6. Center of Regenerative Medicine Washington University School of Medicine St. Louis Missouri USA

7. Department of Biomedical Engineering Washington University School of Engineering and Applied Science St. Louis Missouri USA

8. Shriners Hospitals for Children – St. Louis St. Louis Missouri USA

Abstract

AbstractThis study analyzed knee synovial fluid after anterior cruciate ligament (ACL) tear and in osteoarthritis (OA) to test the hypotheses that concentrations of cytokines, chemokines, and growth factors differ (a) by diagnosis and (b) after ACL tear by time from injury and presence/absence of concomitant meniscus tear. Synovial fluid samples were collected from two groups, ACL tears (with or without meniscus tear) (N = 13) and Kellgren–Lawrence grade 3 and 4 OA (N = 16), undergoing clinically indicated aspiration of the knee joint. Multiple cytokines, chemokines, and growth factors were assessed using a multiplexed 45‐protein panel. Comparisons were made for the concentrations of all molecules between ACL tear and OA patients, isolated versus combined ACL and meniscus tears, and categorized by time from injury: acute or early subacute (<15 days, N = 8) versus late subacute or chronic (>15 days and <3 months, N = 5). ACL tear patients have higher levels of six molecules (IL‐4, IL‐5, IL‐13, PlGF‐1, bNGF, TNF‐α) in knee synovial fluid compared to OA patients. Isolated ACL tears express higher levels of IL‐4, IL‐13 and IFN‐γ and lower levels of IL‐7 than ACL tears with a concomitant meniscus tear. SDF‐1α, PlGF‐1, IL‐1RA, HGF, bNGF, and BDNF levels are elevated immediately after injury and drop off significantly in the late subacute phase (after 15 days). Synovial fluid from knees with ACL tears have elevated metabolic activity compared to knees with OA. The cytokine profiles after ACL tears are influenced by the time from injury and the presence of meniscus tears. These findings offer valuable insights into the levels of cytokines, chemokines, and growth factors in the knee after ACL injury, information which may have important implications for the diagnosis, prognosis and treatment of this common pathology.

Funder

National Institute of Arthritis and Musculoskeletal and Skin Diseases

Publisher

Wiley

Subject

Orthopedics and Sports Medicine

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