Full Text:   <1742>

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CLC number: R684.3

On-line Access: 2020-01-03

Received: 2019-06-27

Revision Accepted: 2019-09-08

Crosschecked: 2019-11-05

Cited: 0

Clicked: 3112

Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Sittisak Honsawek

https://orcid.org/0000-0003-3852-9092

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Journal of Zhejiang University SCIENCE B 2020 Vol.21 No.1 P.42-52

http://doi.org/10.1631/jzus.B1900352


Relationships between blood leukocyte mitochondrial DNA copy number and inflammatory cytokines in knee osteoarthritis


Author(s):  Dong Zhan, Aree Tanavalee, Saran Tantavisut, Srihatach Ngarmukos, Steven W. Edwards, Sittisak Honsawek

Affiliation(s):  Joint PhD Program in Biomedical Sciences and Biotechnology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand; more

Corresponding email(s):   sittisak.h@chula.ac.th

Key Words:  Inflammatory cytokine, Blood leukocyte, Knee, Mitochondrial DNA copy number, Osteoarthritis


Dong Zhan, Aree Tanavalee, Saran Tantavisut, Srihatach Ngarmukos, Steven W. Edwards, Sittisak Honsawek. Relationships between blood leukocyte mitochondrial DNA copy number and inflammatory cytokines in knee osteoarthritis[J]. Journal of Zhejiang University Science B, 2020, 21(1): 42-52.

@article{title="Relationships between blood leukocyte mitochondrial DNA copy number and inflammatory cytokines in knee osteoarthritis",
author="Dong Zhan, Aree Tanavalee, Saran Tantavisut, Srihatach Ngarmukos, Steven W. Edwards, Sittisak Honsawek",
journal="Journal of Zhejiang University Science B",
volume="21",
number="1",
pages="42-52",
year="2020",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1900352"
}

%0 Journal Article
%T Relationships between blood leukocyte mitochondrial DNA copy number and inflammatory cytokines in knee osteoarthritis
%A Dong Zhan
%A Aree Tanavalee
%A Saran Tantavisut
%A Srihatach Ngarmukos
%A Steven W. Edwards
%A Sittisak Honsawek
%J Journal of Zhejiang University SCIENCE B
%V 21
%N 1
%P 42-52
%@ 1673-1581
%D 2020
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1900352

TY - JOUR
T1 - Relationships between blood leukocyte mitochondrial DNA copy number and inflammatory cytokines in knee osteoarthritis
A1 - Dong Zhan
A1 - Aree Tanavalee
A1 - Saran Tantavisut
A1 - Srihatach Ngarmukos
A1 - Steven W. Edwards
A1 - Sittisak Honsawek
J0 - Journal of Zhejiang University Science B
VL - 21
IS - 1
SP - 42
EP - 52
%@ 1673-1581
Y1 - 2020
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1900352


Abstract: 
osteoarthritis (OA) is a degenerative articular disorder manifested by cartilage destruction, subchondral sclerosis, osteophytes, and synovitis, resulting in chronic joint pain and physical disability in the elderly. The purpose of this study was to investigate mitochondrial DNA copy number (mtDNACN) and inflammatory cytokines in primary knee OA patients and healthy volunteers. A total of 204 knee OA patients and 169 age-matched healthy volunteers were recruited. Their relative blood leukocyte mtDNACN was assessed by quantitative real-time polymerase chain reaction (qRT-PCR), and ten inflammatory cytokines in their plasma were detected by multiplex immunoassay. blood leukocyte mtDNACN in the OA group was significantly lower than that in the control group. Leukocyte mtDNACN in the control group was negatively correlated with their age (r=−0.380, P<0.0001), whereas mtDNACN in the OA group was positively correlated with their age (r=0.198, P<0.001). Plasma interleukin-4 (IL-4) and IL-6 were significantly higher in the knee OA group than in the control group. The plasma IL-6 level was positively correlated with blood leukocyte mtDNACN in the OA group (r=0.547, P=0.0014). IL-5 showed as a major factor (coefficient 0.69) in the second dimension of principle components analysis (PCA)-transformed data and was significantly higher in the OA group (P<0.001) as well as negatively correlated with mtDNACN (r=−0.577, P<0.001). These findings suggest that elevation of plasma IL-4 and IL-6 and a relative reduction in mtDNACN might be effective biomarkers for knee OA. IL-5 is a plausible factor responsible for decreasing blood leukocyte mtDNACN in knee OA patients.

膝骨关节炎患者全血白细胞线粒体DNA复制数量和血浆炎性细胞因子的相关性研究

目的:本实验研究全血白细胞线粒体DNA复制数量(mtDNACN)和血浆炎性细胞因子在膝骨关节炎患者中的变化和其相关性.
创新点:探讨了老年(50~80岁)膝骨关节炎患者白细胞mtDNACN和血浆炎性细胞因子水平及二者的关系.
方法:分别收集膝骨关节炎组和对照组血液样本并对膝关节评分(Kellgren-Lawren grading).使用实时定量聚合酶链反应(qRT-PCR)检测相对mtDNACN;使用多重免疫分析(multiplex immunoassay)测定血浆中10种炎性细胞因子水平;应用线性相关、Logistic回归和主成分分析(PCA)揭示骨关节炎白细胞mtDNACN和血浆炎性细胞因子的相关性.
结论:血浆中白介素4(IL-4)、IL-6和全血白细胞mtDNACN可能是膝骨关节炎有效的生物标志物;IL-5则对mtDNACN减少具有潜在的影响.

关键词:炎性细胞因子;血液白细胞;膝关节;线粒体DNA复制数量;骨关节炎

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference

[1]Ashraf MI, Shahzad M, Shabbir A, 2015. Oxyresveratrol ameliorates allergic airway inflammation via attenuation of IL-4, IL-5, and IL-13 expression levels. Cytokine, 76(2):375-381.

[2]Attur M, Statnikov A, Aliferis CF, et al., 2012. Inflammatory genomic and plasma biomarkers predict progression of symptomatic knee OA (SKOA). Osteoarthritis Cartilage, 20(Suppl 1):S34-S35.

[3]Barker T, Rogers VE, Henriksen VT, et al., 2014. Serum cytokines are increased and circulating micronutrients are not altered in subjects with early compared to advanced knee osteoarthritis. Cytokine, 68(2):133-136.

[4]Berenbaum F, 2013. Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!). Osteoarthritis Cartilage, 21(1):16-21.

[5]Blanco FJ, Rego I, Ruiz-Romero C, 2011. The role of mitochondria in osteoarthritis. Nat Rev Rheumatol, 7(3):161-169.

[6]Blanco FJ, Valdes AM, Rego-Pérez I, 2018. Mitochondrial DNA variation and the pathogenesis of osteoarthritis phenotypes. Nat Rev Rheumatol, 14(6):327-340.

[7]Chang YH, Ho KT, Lu SH, et al., 2012. Regulation of glucose/lipid metabolism and insulin sensitivity by interleukin-4. Int J Obes (Lond), 36(7):993-998.

[8]Chawla A, Nguyen KD, Goh YPS, 2011. Macrophage-mediated inflammation in metabolic disease. Nat Rev Immunol, 11(11):738-749.

[9]Chomyn A, Attardi G, 2003. MtDNA mutations in aging and apoptosis. Biochem Biophys Res Commun, 304(3):519-529.

[10]Dechsupa S, Singhatanadgige W, Limthongkul W, et al., 2017. Alterations of relative telomere length and mitochondrial DNA copy number from ligamentum flavum-derived cells in lumbar spinal stenosis: pilot study. Chula Med J, 61(4):497-509.

[11]Fang HZ, Liu XW, Shen LJ, et al., 2014. Role of mtDNA haplogroups in the prevalence of knee osteoarthritis in a southern Chinese population. Int J Mol Sci, 15(2):2646-2659.

[12]Goekoop RJ, Kloppenburg M, Kroon HM, et al., 2010. Low innate production of interleukin-1β and interleukin-6 is associated with the absence of osteoarthritis in old age. Osteoarthritis Cartilage, 18(7):942-947.

[13]Guo SY, Ding YJ, Li L, et al., 2015. Correlation of CD4+ CD25+ Foxp3+ Treg with the recovery of joint function after total knee replacement in rats with osteoarthritis. Genet Mol Res, 14(3):7290-7296.

[14]Hsu FC, Kritchevsky SB, Liu YM, et al., 2009. Association between inflammatory components and physical function in the health, aging, and body composition study: a principal component analysis approach. J Gerontol A Biol Sci Med Sci, 64A(5):581-589.

[15]Kaneko S, Satoh T, Chiba J, et al., 2000. Interleukin-6 and interleukin-8 levels in serum and synovial fluid of patients with osteoarthritis. Cytokines Cell Mol Ther, 6(2):71-79.

[16]Kapoor M, Martel-Pelletier J, Lajeunesse D, et al., 2011. Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat Rev Rheumatol, 7(1):33-42.

[17]Kellgren JH, Lawrence JS, 1957. Radiological assessment of osteo-arthrosis. Ann Rheum Dis, 6(4):494-502.

[18]Kopf M, le Gros G, Bachmann M, et al., 1993. Disruption of the murine IL-4 gene blocks Th2 cytokine responses. Nature, 362(6417):245-248.

[19]Lim KS, Jeyaseelan K, Whiteman M, et al., 2005. Oxidative damage in mitochondrial DNA is not extensive. Ann N Y Acad Sci, 1042(1):210-220.

[20]Liu SF, Kuo HC, Tseng CW, et al., 2015. Leukocyte mitochondrial DNA copy number is associated with chronic obstructive pulmonary disease. PLoS ONE, 10(9):e0138716.

[21]Livak KJ, Schmittgen TD, 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method. Methods, 25(4):402-408.

[22]Livshits G, Zhai GJ, Hart DJ, et al., 2009. Interleukin-6 is a significant predictor of radiographic knee osteoarthritis: the Chingford study. Arthritis Rheum, 60(7):2037-2045.

[23]López-Otín C, Blasco MA, Partridge L, et al., 2013. The hallmarks of aging. Cell, 153(6):1194-1217.

[24]Mabey T, Honsawek S, Tanavalee A, et al., 2016. Plasma and synovial fluid inflammatory cytokine profiles in primary knee osteoarthritis. Biomarkers, 21(7):639-644.

[25]Manoy P, Anomasiri W, Yuktanandana P, et al., 2018. Relationship of serum leptin and 25-hydroxyvitamin D in knee osteoarthritis patients. Chula Med J, 62(6):1037-1047.

[26]Meyer A, Zoll J, Charles AL, et al., 2013. Skeletal muscle mitochondrial dysfunction during chronic obstructive pulmonary disease: central actor and therapeutic target. Exp Physiol, 98(6):1063-1078.

[27]Pedersen BK, Febbraio MA, 2008. Muscle as an endocrine organ: focus on muscle-derived interleukin-6. Physiol Rev, 88(4):1379-1406.

[28]Porée B, Kypriotou M, Chadjichristos C, et al., 2008. Interleukin-6 (IL-6) and/or soluble IL-6 receptor down-regulation of human type II collagen gene expression in articular chondrocytes requires a decrease of Sp1·Sp3 ratio and of the binding activity of both factors to the COL2A1 promoter. J Biol Chem, 283(8):4850-4865.

[29]Schaap LA, Pluijm SMF, Deeg DJH, et al., 2009. Higher inflammatory marker levels in older persons: associations with 5-year change in muscle mass and muscle strength. J Gerontol A Biol Sci Med Sci, 64A(11):1183-1189.

[30]Silvestri T, Pulsatelli L, Dolzani P, et al., 2006. Elevated serum levels of soluble interleukin-4 receptor in osteoarthritis. Osteoarthritis Cartilage, 14(7):717-719.

[31]Smith MD, Triantafillou S, Parker A, et al., 1997. Synovial membrane inflammation and cytokine production in patients with early osteoarthritis. J Rheumatol, 24(2):365-371.

[32]Tanpaisankit M, Hongsaprabhas C, Charoenlap C, et al., 2017. High oxidative stress and decrease of mitochondrial DNA copies in musculoskeletal tumors. Chula Med J, 61(6):771-782.

[33]Thomas NS, Wilkinson J, Holgate ST, 1997. The candidate region approach to the genetics of asthma and allergy. Am J Respir Crit Care Med, 156(4):S144-S151.

[34]Vangsness CT Jr, Burke WS, Narvy SJ, et al., 2011. Human knee synovial fluid cytokines correlated with grade of knee osteoarthritis—a pilot study. Bull NYU Hosp Jt Dis, 69(2):122-127.

[35]Wu IC, Lin CC, Liu CS, et al., 2017. Interrelations between mitochondrial DNA copy number and inflammation in older adults. J Gerontol A Biol Sci Med Sci, 72(7):937-944.

[36]Xing JL, Chen M, Wood CG, et al., 2008. Mitochondrial DNA content: its genetic heritability and association with renal cell carcinoma. J Natl Cancer Inst, 100(15):1104-1112.

[37]Yang YH, Bazhin AV, Werner J, et al., 2013. Reactive oxygen species in the immune system. Int Rev Immunol, 32(3):249-270.

[38]Yousefi S, Gold JA, Andina N, et al., 2008. Catapult-like release of mitochondrial DNA by eosinophils contributes to antibacterial defense. Nat Med, 14(9):949-953.

[39]Zhan D, Honsawek S, 2019. Reduction of leukocyte mitochondrial DNA copy number in knee osteoarthritis. Chula Med J, 63(3):207-209.

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