Correlation of the expression of the inflammatory cytokines
and the pathological degree in patients with knee osteoarthritis

doi:10.3969/j.issn.2095-4344.1916

Abstract

Abstract:

BACKGROUND: In the development of osteoarthritis, the mechanism underlying cartilage damage is still unclear. Matrix metalloproteinases have been shown to play important roles in cartilage matric degradation.

OBJECTIVE: To observe the correlation between the expression of matrix metalloproteinase 3, tissue inhibitor of metalloproteinase-1 and the pathological degree in knee osteoarthritis.

METHODS: The study was approved by the Ethics Committee of Shenyang Orthopedic Hospital. The tibial plateaus of 40 patients with knee osteoarthritis who underwent total knee arthroplasty were collected, and all patients signed the informed consents. The classification of osteoarthritis was evaluated according to Kellgren-Lawrence (KL) scale system: 11 cases of KL grade 2, 15 cases of KL grade 3, and 14 cases of KL grade 4. Control group contained six cases. Samples received hematoxylin-eosin staining. The pathological changes of knee osteoarthritis cartilage were evaluated by Mankin score. Immunohistochemical staining was used to detect the contents of matrix metalloproteinase 3 and tissue inhibitor of metalloproteinase-1 in cartilage.

RESULTS AND CONCLUSION: (1) Hematoxylin-eosin staining results showed that in the control group, the layer of cartilage was thick, and there were abundant chondrocytes that arranged regularly. The subcutaneous layer of cartilage in the KL grade 2 group was rugged, and fissure was observed occasionally. Fibrosis of cartilage layer was visible in the KL grade 3 group, and the chondrocytes arranged in disorder. In the KL grade 4 group, the structure of cartilage layer was lost, and there were few chondrocytes that arranged irregularly. (2) Immunohistochemical staining results showed that the expression level of matrix metalloproteinase 3 in the osteoarthritis group was significantly higher than that in the control group. The expression level of matrix metalloproteinase 3 was on a rise in the KL grade 2, 3 and 4 groups (all P < 0.05). The expression level of tissue inhibitor of metalloproteinase-1 in the osteoarthritis group was significantly lower than that in the control group. The expression level of tissue inhibitor of metalloproteinase-1 was on a descent in the KL grade 2, 3 and 4 groups (all P < 0.05). (3) There was significantly positive correlation between matrix metalloproteinase 3 expression level and Mankin score (r=0.899, P < 0.001), and tissue inhibitor of metalloproteinase-1 expression level was negatively correlated with Mankin score (r=-0.903, P < 0.001). There was significantly negative correlation between tissue inhibitor of metalloproteinase-1 expression level and matrix metalloproteinase 3 expression level (r=-0.881, P < 0.001). (4) These results indicate that in the articular cartilage of patients with osteoarthritis, the expression levels of matrix metalloproteinase 3 and tissue inhibitor of metalloproteinase-1 are correlated with the pathological changes, which can be used as an effective index to evaluate the progress of knee osteoarthritis.

Key words: osteoarthritis, matrix metalloproteinase 3, tissue inhibitor of metalloproteinase-1, Mankin score, correlation analysis

CLC Number:

R496

R684

R318

Wu Bo, Ma Xu, Liu Ye , Wang Yihan, Wang Jiayuan, Li Chongyang, Jiao Dijin. Correlation of the expression of the inflammatory cytokines and the pathological degree in patients with knee osteoarthritis[J]. Chinese Journal of Tissue Engineering Research, 2020, 24(2): 236-241.

Figures/Tables 8

References

[1] 邬波,柳椰,杜明昌,等.膝关节单髁置换治疗膝内侧间室骨关节炎的疗效观察[J].中华骨与关节外科杂志, 2017, 10(2):123-125.
[2] 赵继国.膝关节骨关节炎的治疗进展[J].中医临床研究, 2015, 7(31):144-146.
[3] ACKERMAN IN, BOHENSKY MA, DE STEIGER R, et al. Substantial rise in the lifetime risk of primary total knee replacement surgery for osteoarthritis from 2003 to 2013: an international, population-level analysis. Osteoarthritis Cartilage. 2017;25(4): 455-461.
[4] ACKERMAN I N, ZOMER E, GILMARTIN-THOMAS JF, et al. Forecasting the future burden of opioids for osteoarthritis. Osteoarthritis Cartilage. 2018;26(3):350-355.
[5] SHARIF B, KOPEC J, BANSBACK N, et al.Projecting the direct cost burden of osteoarthritis in Canada using a microsimulation model.Osteoarthritis Cartilage. 2015;23: 1654-1663.
[6] PALAZZO C, NGUYEN C, LEFEVRE-COLAU MM, et al. Risk factors and burden of osteoarthritis.Ann Phys Rehabil Med.2016;59: 134-138.
[7] HÜGLE T, GEURTS J. What drives osteoarthritis?-synovial versus subchondral bone pathology. Rheumatology (Oxford). 2017;56(9):1461-1471.
[8] BERENBAUM F.Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!). Osteoarthritis Cartilage. 2013; 21:16-21.
[9] GEURTS J, PATEL A, HIRSCHMANN MT, et al.Elevated marrow inflammatory cells and osteoclasts in subchondral osteosclerosis in human knee osteoarthritis.J Orthop Res. 2016; 34:262-269.
[10] BAUDART P, LOUATI K, MARCELLI C, et al.Association between osteoarthritis and dyslipidaemia: a systematic literature review and meta-analysis.RMD Open.2017;3: e000442.
[11] ZHANG YM, WANG J, LIU XG.Association between hypertension and risk of knee osteoarthritis: a meta-analysis of observational studies. Medicine(Baltimore).2017;96:e7584.
[12] FRASCA D, BLOMBERG BB, PAGANELLI R.Aging, obesity, and inflammatory age-related diseases. Front Immunol.2017; 8: 1745.
[13] MARTEL-PELLETIER J, PELLETIER JP, CLOUTIER JM, et al. Neutral proteases capable of proteoglycan digesting activity in osteoarthritic and normal human articular cartilage. Arthritis Rheumatol. 1984;27(3):305e12.
[14] DEAN DD, MARTEL-PELLETIER J, PELLETIER JP, et al. Evidence for metalloproteinase and metal-loproteinase inhibitor imbalance in human osteoarthritic cartilage.J Clin Invest.1989;84(2): 678e85.
[15] DOCHERTY AJ, MURPHY G.The tissue metalloproteinase family and the inhibitor TIMP: a study using cDNAs and recombinant proteins. Ann Rheum Dis.1990;49(Suppl 1): 469e79.
[16] CHU XQ, WANG JJ, DOU LD, et al.Cartilage oligomeric matrix protein and matrix metalloproteinase-3 expression in the serum and joint fluid of a reversible osteoarthritis rabbit model. Genet Mol Res. 2015;14(4):14207-14215.
[17] QU H, LI J, WU LD, et al.Trichostatin A increases the TIMP-1/MMP ratio to protect against osteoarthritis in an animal model of the disease. Mol Med Rep. 2016;14(3): 2423-2430.
[18] DULAY GS, COOPER C, DENNISON EM.Knee pain, knee injury, knee osteoarthritis & work. Best Pract Res Clin Rheumatol. 2015; 29(3):454-461.
[19] CUDEJKO T, VAN DER ESCH M, VAN DEN NOORT JC, et al. Decreased pain and improved dynamic knee instability mediate the beneficial effect of wearing a soft knee brace on activity limitations in persons with knee osteoarthritis. Arthritis Care Res (Hoboken). 2018 Aug 12.
[20] ZHENG H, CHEN C.Body mass index and risk of knee osteoarthritis: systematic review and meta-analysis of prospective studies. BMJ Open. 2015;5(12):e007568.
[21] BLAGOJEVIC M, JINKS C, JEFFERY A ,et al.Risk factors for onset of osteoarthritis of the knee in older adults: a systematic review and metaanalysis. Osteoarthritis Cartilage 2010;18 (1): 24-33.
[22] 叶臻,李民,陈定家.骨关节炎软骨下骨的微结构改变[J].中国骨质疏松杂志, 2016,22(5):624-627.
[23] 周嵘,钱齐荣.软骨下骨在骨关节炎发病中作用的研究进展[J].中国矫形外科杂志,2014,22(21):1971-1973.
[24] MADRY H, DIJK C N V, MUELLER-GERBL M.The basic science of subchondral bone.Knee Surgery Sports Traumatology Arthroscopy.2010;18(4):419-433.
[25] JI JB, LI XF, LIU L, et al.Effect of low intensity pulsed ultrasound on expression of TIMP-2 in serum and expression of mmp-13 in articular cartilage of rabbits with knee osteoarthritis. Asian Pac J Trop Med. 2015;8(12):1043-1048.
[26] RAI MF, SCHMIDT EJ, HASHIMOTO S, et al. Genetic loci that regulate ectopic calcification in response to knee trauma in LG/J by SM/J advanced intercross mice.J Orthop Res.2015; 33:1412-1423.
[27] SANCHEZ C, MAZZUCCHELLI G, LAMBERT C, et al. Comparison of secretome from osteoblasts derived from sclerotic versus non-sclerotic subchondral bone in OA: A pilot study.Plos One.2018;13(3):e0194591.
[28] MURPHY G, NAGASE H.Progress in matrix metalloproteinase research.Mol Aspects Med. 2008;29 : 290-308.
[29] JAVAID MA, ABDALLAH MN, AHMED AS, et al.Matrix metalloproteinases and their pathological upregulation in multiple sclerosis: an overview. Acta Neurol Belg.2013; 113:381-390.
[30] FOTOPOULOS VC, TZINIA A, TZURBAKIS M, et al. Expression levels of matrix metalloproteinase (MMP)-9 and its specific inhibitor TIMP-1, in septic and aseptic arthritis of the knee. Knee Surg Sports Traumatol Arthrosc. 2012;20(6): 1159-1167.