Change of inflammatory cytokines levels in both synovial fluid and plasm of patients with primary knee medical osteoarthritis after high tibial osteotomy_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

BAI Yuming ¹ ,  ZHANG Haisen ¹ , LIU Chang ¹ , JIN Shengli ¹ , SU Ke ¹ , LIU Ying ² , LÜ Zhichang ³

1. The Second Department of Orthopaedics, Central Hospital of Cangzhou, Cangzhou Hebei, 061001, P.R.China;
2. Department of Operation Room, People’s Hospital of Cangzhou, Cangzhou Hebei, 061001, P.R.China;
3. Department of Orthopaedics, People’s Hospital of Xianxian, Xianxian Hebei, 062250, P.R.China;

Corresponding author：

ZHANG Haisen, Email: 924699828@qq.com

Keywords：

High tibial osteotomy; osteoarthritis; knee; interleukin-1β; interleukin-6; interleukin-17

DOI：

10.7507/1002-1892.201609123

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Objective To investigate interleukin-1β (IL-1β), IL-6, and IL-17 levels in both synovial fluid and serum of patients with primary knee medial osteoarthritis (OA) after high tbial osteotomy (HTO). Methods Twenty-six patients with primary knee medial OA undergoing HTO between January 2011 and June 2014 (experimental group) and 30 healthy individuals (control group) were recruited into the study. There was no significant difference in gender, age, and body mass index between 2 groups (P>0.05). The X-ray film was taken to record healing time at osteotomy site, to measure the tibiofemoral angle, and to assess limb alignment after HTO. Visual analogue scale (VAS) pain score and knee society score (KSS) were used to evaluate pain level and function of the knee. The IL-1β, IL-6, and IL-17 concentrations in both plasma and synovial fluid were measured before operation and at 6, 12, and 18 months after operation in the experimental group using ELISA method; the levels in plasma were measured in control group. Results Primary healing of incisions was achieved in patients. All patients were followed up 18-24 months (mean, 21 months). The X-ray film showed osseous healing at osteotomy site at 9-14 weeks (mean, 11.5 weeks). The average tibiofemoral angle was 167.5° (range, 165-170°) after bone healing. Satisfactory limb alignment was obtained in all patients. The postoperative VAS pain score was significantly decreased and KSS score was significantly improved when compared with preoperative scores (P<0.05), but no significant difference was found between different time points after operation (P>0.05). The preoperative plasma and synovial fluid IL-1β, IL-6, and IL-17 concentrations were significantly higher in patients than controls (P<0.05). The postoperative IL-1β, IL-6, and IL-17 concentrations in plasma and synovial fluid were significantly lower than preoperative ones in patients (P<0.05), but the concentrations were significantly higher than those in controls (P<0.05). The postoperative plasma and synovial fluid IL-1β, IL-6, and IL-17 concentrations were significantly declined in patients, but there was no significant difference between different time points after operation (P>0.05). Conclusion HTO can significantly improve the pain symptom and joint function and reduce IL-1β, IL-6, and IL-17 levels in both plasma and synovial fluid of patients with medial compartment knee OA, but these cytokines can not return to normal level.

Citation： BAI Yuming, ZHANG Haisen, LIU Chang, JIN Shengli, SU Ke, LIU Ying, LÜ Zhichang. Change of inflammatory cytokines levels in both synovial fluid and plasm of patients with primary knee medical osteoarthritis after high tibial osteotomy. Chinese Journal of Reparative and Reconstructive Surgery, 2017, 31(4): 422-426. doi: 10.7507/1002-1892.201609123 Copy

1.	Cooper BG, Stewart RC, Burstein D, et al. A tissue-penetrating double network restores the mechanical properties of degenerated articular cartilage. Angew Chem Int Ed Engl, 2016, 55(13): 4226-4230.
2.	Honsawek S, Deepaisarnsakul B, Tanavalee A, et al. Association of the IL-6 -174G/C gene polymorphism with knee osteoarthritis in a Thai population. Genet Mol Res, 2011, 10(3): 1674-1680.
3.	Hulin-Curtis SL, Bidwell JL, Perry MJ. Evaluation of IL18 and IL18R1 polymorphisms: genetic susceptibility to knee osteoarthritis. Int J Immunogenet, 2012, 39(2): 106-109.
4.	Sarkar S, Justa S, Brucks M, et al. Interleukin (IL)-17A, F and AF in inflammation: a study in collagen-induced arthritis and rheumatoid arthritis. Clin Exp Immunol, 2014, 177(3): 652-661.
5.	van Baarsen LG, Lebre MC, van der Coelen D, et al. Heterogeneous expression pattern of interleukin 17A (IL-17A), IL-17F and their receptors in synovium of rheumatoid arthritis, psoriatic arthritis and osteoarthritis: possible explanation for nonresponse to anti-IL-17 therapy? Arthritis Res Ther, 2014, 16(4): 426.
6.	Nummenmaa E, Hämäläinen M, Moilanen LJ, et al. Transient receptor potential ankyrin 1 (TRPA1) is functionally expressed in primary human osteoarthritic chondrocytes. Arthritis Res Ther, 2016, 18(1): 185.
7.	Wang K, Xu J, Cai J, et al. Serum levels of resistin and interleukin-17 are associated with increased cartilage defects and bone marrow lesions in patients with knee osteoarthritis. Mod Rheumatol, 2016, 23(Suppl 2): A307.
8.	Wang K, Xu J, Cai J, et al. Serum levels of interleukin-17 and adiponectin are associated with infrapatellar fat pad volume and signal intensity alteration in patients with knee osteoarthritis. Arthritis Res Ther, 2016, 18: 193.
9.	Dallenbach K, Maurer P, Rohn T, et al. Protective effect of a germline, IL-17-neutralizing antibody in murine models of autoimmune inflammatory disease. Eur J Immunol, 2015, 45(4): 1238-1247.
10.	Vinatier C, Merceron C, Guicheux J. Osteoarthritis: from pathogenic mechanisms and recent clinical developments to novel prospective therapeutic options. Drug Discov Today, 2016, 21(12): 1932-1937.
11.	Martimbianco AL, Calabrese FR, Iha LA, et al. Reliability of the "American Knee Society Score" (AKSS). Acta Ortop Bras, 2012, 20(1): 34-38.
12.	Harland NJ, Dawkin MJ, Martin D. Relative utility of a visual analogue scale vs. a six-point Likert scale in the measurement of global subject outcome in patients with low back pain receiving physiotherapy. Physiotherapy, 2015, 101(1): 50-54.
13.	Kraus VB, Nevitt M, Sandell LJ. Summary of the OA biomarkers workshop 2009--biochemical biomarkers: biology, validation, and clinical studies. Osteoarthritis Cartilage, 2010, 18(6): 742-745.
14.	Bondeson J, Wainwright SD, Lauder S, et al. The role of synovial macrophages and macrophage-produced cytokines in driving aggrecanases, matrix metalloproteinases, and other destructive and inflammatory responses in osteoarthritis. Arthritis Res Ther, 2006, 8(6): R187.
15.	Wu X, Kondragunta V, Kornman KS, et al. IL-1 receptor antagonist gene as a predictive biomarker of progression of knee osteoarthritis in a population cohort. Osteoarthritis Cartilage, 2013, 21(7): 930-938.
16.	Haseeb A, Ansari MY, Haqqi TM. Harpagoside suppresses IL-6 expression in primary human osteoarthritis chondrocytes. J Orthop Res, 2017, 35(2): 311-320.
17.	Chen L, Li DQ, Zhong J, et al. IL-17RA aptamer-mediated repression of IL-6 inhibits synovium inflammation in a murine model of osteoarthritis. Osteoarthritis Cartilage, 2011, 19(6): 711-718.
18.	Deligne C, Casulli S, Pigenet A, et al. Differential expression of interleukin-17 and interleukin-22 in inflamed and non-inflamed synovium from osteoarthritis patients. Osteoarthritis Cartilage, 2015, 23(11): 1843-1852.
19.	Jackson JP, Waugh W, Green JP. High tibial osteotomy for osteoarthritis of the knee. J Bone Joint Surg (Br), 1969, 51(1): 88-94.
20.	Hui C, Salmon LJ, Kok A, et al. Long-term survival of high tibial osteotomy for medial compartment osteoarthritis of the knee. Am J Sports Med, 2011, 39(1): 64-70.
21.	Pfahler M, Lutz C, Anetzberger H, et al. Long-term results of high tibial osteotomy for medial osteoarthritis of the knee. Acta Chir Belg, 2003, 103(6): 603-606.
22.	Benzakour T, Hefti A, Lemseffer M, et al. High tibial osteotomy for medial osteoarthritis of the knee: 15 years follow-up. Int Orthop, 2010, 34(2): 209-215.

1. Cooper BG, Stewart RC, Burstein D, et al. A tissue-penetrating double network restores the mechanical properties of degenerated articular cartilage. Angew Chem Int Ed Engl, 2016, 55(13): 4226-4230.
2. Honsawek S, Deepaisarnsakul B, Tanavalee A, et al. Association of the IL-6 -174G/C gene polymorphism with knee osteoarthritis in a Thai population. Genet Mol Res, 2011, 10(3): 1674-1680.
3. Hulin-Curtis SL, Bidwell JL, Perry MJ. Evaluation of IL18 and IL18R1 polymorphisms: genetic susceptibility to knee osteoarthritis. Int J Immunogenet, 2012, 39(2): 106-109.
4. Sarkar S, Justa S, Brucks M, et al. Interleukin (IL)-17A, F and AF in inflammation: a study in collagen-induced arthritis and rheumatoid arthritis. Clin Exp Immunol, 2014, 177(3): 652-661.
5. van Baarsen LG, Lebre MC, van der Coelen D, et al. Heterogeneous expression pattern of interleukin 17A (IL-17A), IL-17F and their receptors in synovium of rheumatoid arthritis, psoriatic arthritis and osteoarthritis: possible explanation for nonresponse to anti-IL-17 therapy? Arthritis Res Ther, 2014, 16(4): 426.
6. Nummenmaa E, Hämäläinen M, Moilanen LJ, et al. Transient receptor potential ankyrin 1 (TRPA1) is functionally expressed in primary human osteoarthritic chondrocytes. Arthritis Res Ther, 2016, 18(1): 185.
7. Wang K, Xu J, Cai J, et al. Serum levels of resistin and interleukin-17 are associated with increased cartilage defects and bone marrow lesions in patients with knee osteoarthritis. Mod Rheumatol, 2016, 23(Suppl 2): A307.
8. Wang K, Xu J, Cai J, et al. Serum levels of interleukin-17 and adiponectin are associated with infrapatellar fat pad volume and signal intensity alteration in patients with knee osteoarthritis. Arthritis Res Ther, 2016, 18: 193.
9. Dallenbach K, Maurer P, Rohn T, et al. Protective effect of a germline, IL-17-neutralizing antibody in murine models of autoimmune inflammatory disease. Eur J Immunol, 2015, 45(4): 1238-1247.
10. Vinatier C, Merceron C, Guicheux J. Osteoarthritis: from pathogenic mechanisms and recent clinical developments to novel prospective therapeutic options. Drug Discov Today, 2016, 21(12): 1932-1937.
11. Martimbianco AL, Calabrese FR, Iha LA, et al. Reliability of the "American Knee Society Score" (AKSS). Acta Ortop Bras, 2012, 20(1): 34-38.
12. Harland NJ, Dawkin MJ, Martin D. Relative utility of a visual analogue scale vs. a six-point Likert scale in the measurement of global subject outcome in patients with low back pain receiving physiotherapy. Physiotherapy, 2015, 101(1): 50-54.
13. Kraus VB, Nevitt M, Sandell LJ. Summary of the OA biomarkers workshop 2009--biochemical biomarkers: biology, validation, and clinical studies. Osteoarthritis Cartilage, 2010, 18(6): 742-745.
14. Bondeson J, Wainwright SD, Lauder S, et al. The role of synovial macrophages and macrophage-produced cytokines in driving aggrecanases, matrix metalloproteinases, and other destructive and inflammatory responses in osteoarthritis. Arthritis Res Ther, 2006, 8(6): R187.
15. Wu X, Kondragunta V, Kornman KS, et al. IL-1 receptor antagonist gene as a predictive biomarker of progression of knee osteoarthritis in a population cohort. Osteoarthritis Cartilage, 2013, 21(7): 930-938.
16. Haseeb A, Ansari MY, Haqqi TM. Harpagoside suppresses IL-6 expression in primary human osteoarthritis chondrocytes. J Orthop Res, 2017, 35(2): 311-320.
17. Chen L, Li DQ, Zhong J, et al. IL-17RA aptamer-mediated repression of IL-6 inhibits synovium inflammation in a murine model of osteoarthritis. Osteoarthritis Cartilage, 2011, 19(6): 711-718.
18. Deligne C, Casulli S, Pigenet A, et al. Differential expression of interleukin-17 and interleukin-22 in inflamed and non-inflamed synovium from osteoarthritis patients. Osteoarthritis Cartilage, 2015, 23(11): 1843-1852.
19. Jackson JP, Waugh W, Green JP. High tibial osteotomy for osteoarthritis of the knee. J Bone Joint Surg (Br), 1969, 51(1): 88-94.
20. Hui C, Salmon LJ, Kok A, et al. Long-term survival of high tibial osteotomy for medial compartment osteoarthritis of the knee. Am J Sports Med, 2011, 39(1): 64-70.
21. Pfahler M, Lutz C, Anetzberger H, et al. Long-term results of high tibial osteotomy for medial osteoarthritis of the knee. Acta Chir Belg, 2003, 103(6): 603-606.
22. Benzakour T, Hefti A, Lemseffer M, et al. High tibial osteotomy for medial osteoarthritis of the knee: 15 years follow-up. Int Orthop, 2010, 34(2): 209-215.

Chinese Journal of Reparative and Reconstructive Surgery

Change of inflammatory cytokines levels in both synovial fluid and plasm of patients with primary knee medical osteoarthritis after high tibial osteotomy

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