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

Dong Zhan; Aree Tanavalee; Saran Tantavisut; Srihatach Ngarmukos; Steven W Edwards; Sittisak Honsawek

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

Author: Dong ZHAN ¹ ; Aree TANAVALEE ² ; Saran TANTAVISUT ² ; Srihatach NGARMUKOS ² ; Steven W EDWARDS ³ ; Sittisak HONSAWEK ⁴
Author Information

1. Joint PhD Program in Biomedical Sciences and Biotechnology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.
2. Department of Orthopaedics, Vinai Parkpian Orthopaedic Research Center, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Chulalongkorn University, Bangkok 10330, Thailand.
3. Institute of Integrative Biology, University of Liverpool, Liverpool L69 7ZB, UK.
4. Department of Biochemistry, Osteoarthritis and Musculoskeleton Research Unit, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Chulalongkorn University, Bangkok 10330, Thailand.
Publication Type:Journal Article
Keywords: Inflammatory cytokine; Blood leukocyte; Knee; Mitochondrial DNA copy number; Osteoarthritis
MeSH: Age Factors; Aged; Aged, 80 and over; Cytokines/blood*; DNA, Mitochondrial/blood*; Female; Gene Dosage; Humans; Leukocytes/metabolism*; Male; Middle Aged; Osteoarthritis, Knee/metabolism*; Principal Component Analysis
From: Journal of Zhejiang University. Science. B 2020;21(1):42-52
CountryChina
Language:English
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 (mtDNA_CN) 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 mtDNA_CN 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 mtDNA_CN in the OA group was significantly lower than that in the control group. Leukocyte mtDNA_CN in the control group was negatively correlated with their age (r=-0.380, P<0.0001), whereas mtDNA_CN 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 mtDNA_CN 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 mtDNA_CN (r=-0.577, P<0.001). These findings suggest that elevation of plasma IL-4 and IL-6 and a relative reduction in mtDNA_CN might be effective biomarkers for knee OA. IL-5 is a plausible factor responsible for decreasing blood leukocyte mtDNA_CN in knee OA patients.