Expression and correlation of matrix metalloproteinase-3 and galectin-3 in synovial tissue of osteoarthritis patients

doi:10.3969/j.issn.2095-4344.1222

Abstract

Abstract:

BACKGROUND: Matrix metalloproteinase-3 and galectin-3 play important roles in the pathological process of osteoarthritis. There may be some potential relationship between them, but has not been reported.
OBJECTIVE: To detect the expression levels of matrix metalloproteinase-3 and galectin-3 in the synovial tissue of osteoarthritis, and to investigate the roles and relationship between matrix metalloproteinase-3 and galectin-3 in the pathogenesis of osteoarthritis.
METHODS: Synovial tissues were obtained from the 60 patients undergoing total knee arthroplasty or knee arthroscopic treatment surgery and 20 healthy patients suffering from amputation caused by trauma or meniscus or knee ligament injuries caused by acute injury. The informed consents were obtained from all patients, and the study was approved by the Ethics Committee of First Affiliated Hospital of Medical College of Shihezi University. According to the Western Ontario and McMaster Universities Osteoarthritis Index, the osteoarthritis observation group was divided into three groups: mild, moderate, and severe groups, with 20 cases in each group. The expression levels of matrix metalloproteinase-3 and galectin-3 in the synovial tissues were detected by immunohistochemistry, and Pearson correlation analysis was conducted.
RESULTS AND CONCLUSION: (1) Immunohistochemistry results showed that matrix metalloproteinase-3 was positive in 2 (10%) in the non-osteoarthritis group, positive in 7 (35%) samples in the mild-osteoarthritis group, positive in 13 (65%) samples in the medium-osteoarthritis group and positive in 18 (90%) samples in the severe-osteoarthritis group. (2) Galectin-3 was positive in 1 (5%) sample in the non-osteoarthritis group, positive in 6 (30%) samples in the mild-osteoarthritis group, positive in 12 (60%) samples in the medium-osteoarthritis group and positive in 17 (85%) samples in the severe-osteoarthritis group. (3) The expression levels of matrix metalloproteinase-3 and galectin-3 in the synovial tissues presented a positive correlation (r=0.926, P < 0.001), and the levels increased with joint degeneration becoming severe. (4) These results imply that there is a significant increase in the expression levels of matrix metalloproteinase-3 and galectin-3 in the synovial tissues of osteoarthritis compared with the non-osteoarthritis group, and both exert effect in osteoarthritis. Matrix metalloproteinase-3 and galectin-3 play important roles in regulating the process of osteoarthritis and related mutually, thus providing new theoretical direction and experimental basis for targeted gene therapy of osteoarthritis.

Key words: matrix metalloproteinase-3, galectin-3, knee arthroplasty, knee arthroscope, osteoarthritis, synovial membrane, the National Natural Science Foundation of China

CLC Number:

R459.9

Yang Pengfei, Gao Peng, Li Yuejun, Jian Yongzhi, Yang Tong, Gu Peilun, Wang Weishan, Dong Jinbo. Expression and correlation of matrix metalloproteinase-3 and galectin-3 in synovial tissue of osteoarthritis patients [J]. Chinese Journal of Tissue Engineering Research, 2019, 23(23): 3616-3622.

Figures/Tables 4

2.3 免疫组化法检测滑膜组织中基质金属蛋白酶3的表达非骨关节炎对照组中基质金属蛋白酶3表达阳性2例，阳性率为10%。骨关节炎观察组(轻、中、重度)患者滑膜组织中的基质金属蛋白酶3表达，轻度骨关节炎观察组阳性7例，阳性率为35%；中度骨关节炎观察组阳性13例，阳性率为65%；重度骨关节炎观察组阳性18例，阳性率为90%。通过连续校正卡方检验进行统计学分析，结果提示骨关节炎观察组与非骨关节炎对照组基质金属蛋白酶3表达差异有显著性意义(P < 0.001)；中、重度骨关节炎观察组与非骨关节炎对照组差异有显著性意义(P < 0.001)，轻度骨关节炎观察组与非骨关节炎对照组差异无显著性意义(P=0.130)；轻、中、重度骨关节炎观察组相互比较，除轻度与重度组差异有显著性意义外(P< 0.05)，其余各组间比较，差异均无显著性意义[P分别为0.114(轻&中)，0.130(中&重)]，见表3。基质金属蛋白酶3染色见图1。 2.4 免疫组化检测滑膜组织中半乳糖凝集素3的表达非骨关节炎对照组滑膜组织中半乳糖凝集素3阳性表达1例，阳性率为5%。骨关节炎观察组(轻、中、重度)患者滑膜组织中的半乳糖凝集素3阳性表达，轻度骨关节炎观察组6例，阳性率为30%；中度骨关节炎观察组12例，阳性率为60%；重度骨关节炎观察组17例，阳性率为85%。用连续校正卡方检验进行统计学分析，结果表明骨关节炎观察组与非骨关节炎对照组半乳糖凝集素3表达差异有显著性意义(P < 0.001)；各组间两两比较，非骨关节炎对照组与轻度骨关节炎观察组之间差异无显著性意义(P=0.096)；中、重度骨关节炎观察组阳性表达率明显高于非骨关节炎对照组，差异有显著性意义(P < 0.001)；轻、中、重度骨关节炎组两两组间相互比较，轻度与重度组差异有显著性意义(P < 0.05)，轻度与中度、中度与重度比较，差异均无显著性意义[P分别为0.112(轻&中)，0.157(中&重)]，见表3。半乳糖凝集素3染色见图1。"

References

[1]Loeser RF. Aging processes and the development of osteoarthritis. Curr Opin Rheumatol. 2013;25(1): 108-113.

[2]Davis AM, MacKay C. Osteoarthritis year in review: outcome of rehabilitation. Osteoarthritis Cartilage. 2013; 21(10): 1414-1424.

[3]王斌,邢丹,董圣杰,等. 中国膝骨关节炎流行病学和疾病负担的系统评价[J]. 中国循证医学杂志,2018,18(2):134-142.

[4]Li Y, Wei X, Zhou J, et al. The age-related changes in cartilage and osteoarthritis. Biomed Res Int. 2013;2013: 916530.

[5]钱佳慧,吴侃,罗会强,等. 中国老年人日常生活活动能力损失现况及影响因素分析[J]. 中华流行病学杂志,2016,37(9): 1272-1276.

[6]Milner JM, Patel A, Davidson RK, et al. Matriptase is a novel initiator of cartilage matrix degradation in osteoarthritis. Arthritis Rheum. 2010;62(7): 1955-66.

[7]Murphy G, Lee MH. What are the roles of metalloproteinases in cartilage and bone damage. Ann Rheum Dis. 2005;64 Suppl 4: iv44-47.

[8]Malemud CJ. Matrix Metalloproteinases and Synovial Joint Pathology. Prog Mol Biol Transl Sci. 2017; 148: 305-325.

[9]马丽艳,宋旭东,张德新,等. MMP-13和 Galectin-3在骨性关节炎滑膜组织中的临床意义[J]. 中国骨与关节杂志, 2013,(5): 280-284.

[10]Yu Q, Shen W, Zhou H, et al. Knockdown of LI-cadherin alters expression of matrix metalloproteinase-2 and -9 and galectin-3. Mol Med Rep. 2016;13(5):4469-4474.

[11]Wang YG, Kim SJ, Baek JH, et al. Galectin-3 increases the motility of mouse melanoma cells by regulating matrix metalloproteinase-1 expression. Exp Mol Med. 2012;44(6): 387-393.

[12]Che ATNA, Lau SF, Mohamed S. Ficus deltoidea Prevented Bone Loss in Preclinical Osteoporosis/Osteoarthritis Model by Suppressing Inflammation. Calcif Tissue Int. 2018;103(4): 388-399.

[13]中华医学会骨科学分会.骨关节炎诊治指南(2007年版)[J]. 中国矫形外科杂志, 2014,22(3):287-288.

[14]庞坚,曹月龙,陈博,等. 基于WOMAC与AIMS2-SF评分的膝骨关节炎主症与生存质量的多元线性回归分析[J]. 中国中医骨伤科杂志, 2013,21(9):13-14,30.

[15]Christoforakis JJ, Sanchez-Ballester J, Hunt N, et al. Synovial shelves of the knee: association with chondral lesions. Knee Surg Sports Traumatol Arthrosc. 2006;14(12):1292-1298.

[16]于萍,步宏,王华,等. 免疫组化结果的图像分析与人工计数方法的对比研究[J]. 生物医学工程学杂志,2003,20(2):288-290.

[17]Scanzello CR, Goldring SR. The role of synovitis in osteoarthritis pathogenesis. Bone. 2012;51(2):249-257.

[18]Sokolove J, Lepus CM. Role of inflammation in the pathogenesis of osteoarthritis: latest findings and interpretations. Ther Adv Musculoskelet Dis. 2013;5(2):77.

[19]Meszaros E, Malemud CJ. Prospects for treating osteoarthritis: enzyme-protein interactions regulating matrix metalloproteinase activity. Ther Adv Chronic Dis. 2012;3(5): 219-229.

[20]李龙滕,李彦林,王坤,等. TN14003体外阻断SDF-1/CXCR4信号通路对骨关节炎患者软骨组织分泌基质金属蛋白酶3、9、13水平的影响[J]. 中国运动医学杂志,2017,36(1):44-47.

[21]朱新辉,徐大伟,黄巍,等. 膝关节骨性关节炎血液和滑液MMP-3水平与其病变程度的相关性[J]. 中国骨质疏松杂志, 2013,19(3): 203-206.

[22]刘琳琳,傅捷,张树明,等. IL-6联合 MMP-3在早期诊断骨性关节炎中表达及临床意义[J]. 中国实验诊断学, 2017,21(2): 273-276.

[23]Melo FH, Butera D, Junqueira MS, et al. The promigratory activity of the matricellular protein galectin-3 depends on the activation of PI-3 kinase. PLoS One. 2011;6(12):e29313.

Janelle-Montcalm A, Boileau C, Poirier F, et al. Extracellular localization of galectin-3 has a deleterious role in joint tissues. Arthritis Res Ther. 2007;9(1):R20.