journal article·2021-07-31Open access

Genetic Deletion of Interleukin-15 Is Not Associated with Major Structural Changes Following Experimental Post-Traumatic Knee Osteoarthritis in Rats

Ermina Hadzic, Garth Blackler, Holly Dupuis, Stephen James Renaud, Christopher Thomas Appleton, Frank Beier

Applied Sciences· Volume 11· Issue 15

Abstract

Post-traumatic osteoarthritis (PTOA) is a degenerative joint disease, leading to articular cartilage breakdown, osteophyte formation, and synovitis, caused by an initial joint trauma. Pro-inflammatory cytokines increase catabolic activity and may perpetuate inflammation following joint trauma. Interleukin-15 (IL-15), a pro-inflammatory cytokine, is increased in OA patients, although its roles in PTOA pathophysiology are not well characterized. Here, we utilized Il15 deficient rats to examine the role of IL-15 in PTOA pathogenesis in an injury-induced model. OA was surgically induced in Il15 deficient Holtzman Sprague-Dawley rats and control wild-type rats to compare PTOA progression. Semi-quantitative scoring of the articular cartilage, subchondral bone, osteophyte size, and synovium was performed by two blinded observers. There was no significant difference between Il15 deficient rats and wild-type rats following PTOA-induction across articular cartilage damage, subchondral bone damage, and osteophyte scoring. Similarly, synovitis scoring across six parameters found no significant difference between genetic variants. Overall, IL-15 does not appear to play a key role in the development of structural changes in this surgically-induced rat model of PTOA.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Osteoarthritis Treatment and Mechanisms · Knee injuries and reconstruction techniques · Lower Extremity Biomechanics and Pathologies

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Physiology and Pharmacology, Schulich School of Medicine & Dentistry, Western University, 1151 Richmond St., London, ON N6A 3K7, Canada

Bone and Joint Institute, Western University, 1151 Richmond St., London, ON N6A 3K7, Canada

Department of Microbiology and Immunology, Schulich School of Medicine & Dentistry, Western University, 1151 Richmond St., London, ON N6A 3K7, Canada

Department of Anatomy and Cell Biology, Schulich School of Medicine & Dentistry, Western University, 1151 Richmond St., London, ON N6A 3K7, Canada

Department of Medicine, Schulich School of Medicine & Dentistry, Western University, 1151 Richmond St., London, ON N6A 3K7, Canada

References (39)

Show source-provided references
1. Global, regional and national burden of osteoarthritis 1990–2017: A systematic analysis of the Global Burden of Disease Study 201710.1136/annrheumdis-2019-216515 ↗
2. Osteoarthritis Cartilage (2021, March 12). Standardization of Osteoarthritis Definitions. Available online: https://oarsi.org/research/standardization-osteoarthritis-definitions.
3. Epidemiology of posttraumatic osteoarthritis10.4085/1062-6050-51.5.08 ↗
4. Posttraumatic osteoarthritis: A first estimate of in-cidence, prevalence, and burden of disease10.1097/01.bot.0000246468.80635.ef ↗
5. Inflammation in joint injury and post-traumatic osteoarthritis10.1016/j.joca.2015.08.015 ↗
6. Evolving concepts of rheumatoid arthritis10.1038/nature01661 ↗
7. Low-grade inflammation as a key mediator of the pathogenesis of osteoarthritis10.1038/nrrheum.2016.136 ↗
8. Role of proinflammatory cytokines in the pathophysiology of osteoarthritis10.1038/nrrheum.2010.196 ↗
9. The normal synovium10.2174/1874312901105010100 ↗
10. Martel-Pelletier, J., Lajeunesse, D., and Pelletier, J.P. (2005). Arthritis and Allied Conditions: A Textbook of Rheumatology, Lippincott Williams & Wilkins. [15th ed.].
11. The role of inflammatory and anti-inflammatory cytokines in the pathogenesis of osteoarthritis10.1155/2014/561459 ↗
12. The role of matrix metalloproteinases in osteoarthritis pathogenesis: An updated review10.1016/j.lfs.2019.116786 ↗
13. Cytokine and cytokine receptor pleiotropy and redundancy10.1074/jbc.R200003200 ↗
14. The joint synovium: A critical determinant of articular cartilage fate in inflammatory joint diseases10.1016/j.semcdb.2016.05.009 ↗
15. Interleukin 15: Biology and relevance to human disease10.1182/blood.V97.1.14 ↗
16. Interleukin 15: A key cytokine for immunotherapy10.1016/j.cytogfr.2016.06.001 ↗
17. IL15RA is required for osteoblast function and bone mineralization10.1016/j.bone.2017.06.003 ↗
18. Inhibition of T cell-dependent and RANKL-dependent osteoclastogenic processes associated with high levels of bone mass in interleukin-15 receptor-deficient mice10.1002/art.27645 ↗
19. Interleukin-15 and interleukin-15Rα SNPs and associations with muscle, bone, and predictors of the metabolic syndrome10.1016/j.cyto.2008.04.008 ↗
20. Therapeutic potential of IL-15 in rheumatoid arthritis10.1016/j.humimm.2015.09.041 ↗
21. Expression and correlation of matrix metalloproteinase-7 and interleukin-15 in human osteoarthritis
22. Local cytokine profiles in knee osteoarthritis: Elevated synovial fluid interleukin-15 differentiates early from end-stage disease10.1016/j.joca.2009.02.011 ↗
23. IL-15 and IL15RA in osteoarthritis: Association with symptoms and protease production, but not structural severity10.3389/fimmu.2020.01385 ↗
24. Serum interleukin-15 levels are associated with severity of pain in patients with knee osteoarthritis10.1155/2013/176278 ↗
25. Elevated plasma and synovial fluid interleukin-8 and interleukin-18 may be associated with the pathogenesis of knee osteoarthritis10.1016/j.knee.2019.10.028 ↗
26. Natural killer-cell deficiency alters placental development in rats†10.1095/biolreprod.116.142752 ↗
27. Forced mobilization accelerates pathogenesis: Characterization of a preclinical surgical model of osteoarthritis10.1186/ar2120 ↗
28. The OARSI histopathology initiative—Recommendations for histological assessments of osteoarthritis in the rat10.1016/j.joca.2010.05.030 ↗
29. Reduction in disease progression by inhibition of transforming growth factor α-CCL2 signaling in experimental posttraumatic osteoarthritis10.1002/art.39255 ↗
30. Exploring longitudinal associations of histologically assessed inflammation with symptoms and radiographic damage in knee osteoarthritis: Com-bined results of three prospective cohort studies10.1016/j.joca.2018.10.014 ↗
31. The measurement of observer agreement for categorical data10.2307/2529310 ↗
32. Reversible defects in natural killer and memory Cd8 T cell lineages in interleukin 15–deficient mice10.1084/jem.191.5.771 ↗
33. IL-15 regulates fibrosis and inflammation in a mouse model of chronic pancreatitis10.1152/ajpgi.00139.2018 ↗
34. IL-15 Receptor deletion results in circadian changes of locomotor and metabolic activity10.1007/s12031-009-9319-z ↗
35. Loss of IL-15 receptor α alters the endurance, fatigability, and metabolic characteristics of mouse fast skeletal muscles10.1172/JCI44945 ↗
36. Lacraz, G., Rakotoarivelo, V., Labbé, S.M., Vernier, M., Noll, C., and Mayhue, M. (2016). Deficiency of interleukin-15 confers resistance to obesity by diminishing inflammation and enhancing the thermogenic function of adipose tissues. PLoS ONE, 11.10.1371/journal.pone.0166537 ↗
37. Synovial tissue-infiltrating natural killer cells in osteo-arthritis and periprosthetic inflammation10.1002/art.27751 ↗
38. CD56+/CD16− natural killer cells expressing the inflammatory protease granzyme A are enriched in synovial fluid from patients with osteoarthritis10.1016/j.joca.2017.06.007 ↗
39. Biomechanical characterization of a model of noninvasive, traumatic anterior cruciate ligament injury in the rat10.1007/s10439-015-1292-9 ↗