Increased expression of damage-associated molecular patterns (DAMPs) in osteoarthritis of human knee joint compared to hip joint
- 342 Downloads
Osteoarthritis (OA) is a degenerative disease characterized by the destruction of cartilage. The greatest risk factors for the development of OA include age and obesity. Recent studies suggest the role of inflammation in the pathogenesis of OA. The two most common locations for OA to occur are in the knee and hip joints. The knee joint experiences more mechanical stress, cartilage degeneration, and inflammation than the hip joint. This could contribute to the increased incidence of OA in the knee joint. Damage-associated molecular patterns (DAMPs), including high-mobility group box-1, receptor for advanced glycation end products, and alarmins (S100A8 and S100A9), are released in the joint in response to stress-mediated chondrocyte and cartilage damage. This facilitates increased cartilage degradation and inflammation in the joint. Studies have documented the role of DAMPs in the pathogenesis of OA; however, the comparison of DAMPs and its influence on OA has not been discussed. In this study, we compared the DAMPs between OA knee and hip joints and found a significant difference in the levels of DAMPs expressed in the knee joint compared to the hip joint. The increased levels of DAMPs suggest a difference in the underlying pathogenesis of OA in the knee and the hip and highlights DAMPs as potential therapeutic targets for OA in the future.
KeywordsOsteoarthritis Hip joint Knee joint HMGB-1 RAGE S100A8 S100A9
This work was supported by research Grants R01 HL112597, R01 HL116042, and R01 HL120659 to DK Agrawal from the National Heart, Lung and Blood Institute, National Institutes of Health, USA. The content of this review article is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Conception and design: VR, MFD, and DKA; contributed reagents/materials/analysis tool: MFD, TDS, and DKA; analysis and interpretation of the data: JHR and VR; drafting of the manuscript: JHR, VR, MFD, TDS, and DKA; critical revision of the article for important intellectual content: VR, MFD, and DKA; final approval of the article: JHR, VR, MFD, TDS, and DKA.
Compliance with ethical standards
Conflict of interest
As the corresponding author, I declare that this manuscript is original, that the article does not infringe upon any copyright or other proprietary rights of any third party, and that neither the text nor the data have been reported or published previously. All the authors have no conflict of interest and have read the journal’s authorship statement.
- 5.Attur M, Belitskaya-Lévy I, Oh C, Krasnokutsky S, Greenberg J, Samuels J, Smiles S, Lee S, Patel J, Al-Mussawir H, McDaniel G, Kraus VB, Abramson SB (2011) Increased interleukin-1β gene expression in peripheral blood leukocytes is associated with increased pain and predicts risk for progression of symptomatic knee osteoarthritis. Arthritis Rheumatol 63(7):1908–1917CrossRefGoogle Scholar
- 12.Rasheed Z, Akhtar N, Haqqi TM (2011) Advanced glycation end products induce the expression of interleukin-6 and interleukin-8 by receptor for advanced glycation end product-mediated activation of mitogen-activated protein kinases and nuclear factor-kappaB in human osteoarthritis chondrocytes. Rheumatology 50(5):838–851CrossRefPubMedGoogle Scholar
- 19.Hamada T, Torikai M, Kuwazuru A, Tanaka M, Horai N, Fukuda T, Yamada S, Nagayama S, Hashiguchi K, Sunahara N, Fukuzaki K, Nagata R, Komiya S, Maruyama I, Fukuda T, Abeyama K (2008) Extracellular high mobility group box chromosomal protein 1 is a coupling factor for hypoxia and inflammation in arthritis. Arthritis Rheumatol 58(9):2675–2685CrossRefGoogle Scholar
- 24.Sunahori K, Yamamura M, Yamana J, Takasugi K, Kawashima M, Yamamoto H, Chazin WJ, Nakatani Y, Yui S, Makino H (2006) The S100A8/A9 heterodimer amplifies proinflammatory cytokine production by macrophages via activation of nuclear factor kappa B and p38 mitogen-activated protein kinase in rheumatoid arthritis. Arthritis Res Ther 8(3):R69CrossRefPubMedPubMedCentralGoogle Scholar
- 29.van Lent PL, Blom AB, Schelbergen RF, Sloetjes A, Lafeber FP, Lems WF, Cats H, Vogl T, Roth J, van den Berg WB (2012) Active involvement of alarmins S100A8 and S100A9 in the regulation of synovial activation and joint destruction during mouse and human osteoarthritis. Arthritis Rheumatol 64(5):1466–1476CrossRefGoogle Scholar
- 34.Schelbergen RF, Blom AB, van den Bosch MH, Slöetjes A, Abdollahi-Roodsaz S, Schreurs BW, Mort JS, Vogl T, Roth J, van den Berg WB, van Lent PL (2012) Alarmins S100A8 and S100A9 elicit a catabolic effect in human osteoarthritic chondrocytes that is dependent on Toll-like receptor 4. Arthritis Rheumatol 64(5):1477–1487CrossRefGoogle Scholar