Down-regulated Leptin Receptor by Small Interfering RNA Inhibits the Messenger RNA Expressions of Interleukin-1β and Nitric Oxide of Human Osteoarthritis Chondrocytes_West China Medical Journal

Authors：

 TangXin , Zhengguo , ChenZhuo , HuangQiang , LiQi , FuWeili ,  LiJian , ChenGang , ZhouZongke , PeiFuxing

Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;
2. Science and Technology Park, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding author：

LiJian, Email: hxlijian.china@163.com

Keywords：

Osteoarthritis; Human chondrocytes; Small interfering RNA; Interleukin-1β; Nitric oxide

DOI：

10.7507/1002-0179.201600233

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To study the effect of down-regulated leptin receptor by small interfering RNA (siRNA) in inhibiting the messenger RNA (mRNA) expressions of interleukin (IL)-1β and nitric oxide (NO) of human osteoarthritis chondrocytes, in order to provide reference for basic clinical research. Methods Cartilage was harvested under sterile conditions from osteoarthritis knee joints in patients undergoing total knee arthroplasty. Human articular chondrocytes were isolated and the cells were cultured in vitro. The cells in the 3rd passage were transferred by siRNA Ob-Rb (experimental group) and blank Ob-Rb (control group), respectively. Then mRNA expressions of IL-1β and NO were tested by quantitative polymerase chain reaction at hour 24, 48 and 72 after successful transfection. Results The mRNA expressions of IL-1β increased slightly and that of NO declined slightly at hour 24, 48 and 72 after transfection in the treatment group, but they all were significantly lower than those in the control group (P ＜ 0.05) , and the differences became much larger as time went on. Conclusion Leptin receptor under siRNA technology can significantly inhibit the mRNA expressions of IL-1β and NO in human osteoarthritis chondrocytes.

Citation： TangXin, Zhengguo, ChenZhuo, HuangQiang, LiQi, FuWeili, LiJian, ChenGang, ZhouZongke, PeiFuxing. Down-regulated Leptin Receptor by Small Interfering RNA Inhibits the Messenger RNA Expressions of Interleukin-1β and Nitric Oxide of Human Osteoarthritis Chondrocytes. West China Medical Journal, 2016, 31(5): 854-858. doi: 10.7507/1002-0179.201600233 Copy

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16.	Koskinen A, Juslin S, Nieminen R, et al. Adiponectin associates with markers of cartilage degradation in osteoarthritis and induces production of proinflammatory and catabolic factors through mitogen-activated protein kinase pathways[J]. Arthritis Res Ther, 2011, 13(6) : R184.
17.	Iliopoulos D, Malizos KN, Tsezou A. Epigenetic regulation of leptin affects MMP-13 expression in osteoarthritic chondrocytes: possible molecular target for osteoarthritis therapeutic intervention[J]. Ann Rheum Dis, 2007, 66(12) : 1616-1621.
18.	Tong KM, Shieh DC, Chen CP, et al. Leptin induces IL-8 expression via leptin receptor, IRS-1, PI3K, Akt cascade and promotion of NFkappaB/ p300 binding in human synovial fibroblasts[J]. Cell Signal, 2008, 20(8) : 1478-1488.
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20.	Presle N, Pottie P, Dumond H, et al. Differential distribution of adipokines between serum and synovial fluid in patients with osteoarthritis. Contribution of joint tissues to their articular production[J]. Osteoarthrit Cartil, 2006,14(7) : 690-695.

1. Creamer P, Hochberg MC. Osteoarthritis[J]. Lancet, 1997, 350(9076) : 503-508.
2. Isogai N, Kusuhara H, Ikada Y, et al. Comparison of different chondrocytes for use in tissue engineering of cartilage model structures[J]. Tissue Eng, 2006, 12(4) : 691-703.
3. Alsalameh S, Amin R, Gemba T, et al. Identification of mesenchymal progenitor cells in normal and osteoarthritic human articular cartilage[J]. Arthritis Rheum, 2004, 50(5) : 1522-1532.
4. Felson DT, Kim YJ. The futility of current approaches to chondroprotection[J]. Arthritis Rheum, 2007, 56(5) : 1378-1383.
5. Samuels J, Krasnokutsky S, Abramson SB. Osteoarthritis: a tale of three tissues[J]. Bull NYU Hosp Jt Dis, 2008, 66(3) : 244-250.
6. Adamczak M, Wiecek A. The adipose tissue as an endocrine organ[J]. Semin Nephrol, 2013, 33(1) : 2-13.
7. Gabay O, Berenbaum F. Adipokines in arthritis: new Kids on the block[J]. Curr Rheumatol Rev, 2009, 5(4) : 226-232.
8. Otero M, Lago R, Lago F, et al. Signalling pathway involved in nitric oxide synthase type Ⅱ activation in chondrocytes: synergistic effect of leptin with interleukin-1[J]. Arthritis Res Ther, 2005, 7(3) : R581-R591.
9. Conde J, Scotece M, Gómez R, et al. Adipokinesand osteoarthritis: novel molecules involved in the pathogenesis and progression of disease[J]. Arthritis, 2011(2011) : 203901.
10. Yang WH, Liu SC, Tsai CH, et al. Leptin induces IL-6 expression through OBRl receptor signaling pathway in human synovial fibroblasts[J]. PLoS One, 2013, 8(9) : e75551.
11. Scotece M, Conde J, López V, et al. Adiponectin and leptin: new targets in inflammation [J]. Basic Clin Pharmacol Toxicol, 2014, 114(1) : 97-102.
12. Altman R, Asch E, Bloch D, et al. Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association[J]. Arthritis Rheum, 1986, 29(8) : 1039-1049.
13. Loeser RF. Systemic and local regulation of articular cartilage metabolism: where does leptin fit in the puzzle?[J]. Arthrit Rheumat, 2003, 48(11) : 3009-3012.
14. Simopoulou T, Malizos KN, Iliopoulos D, et al. Differential expression of leptin and leptin’s receptor isoform (Ob-Rb) mRNA between advanced and minimally affected osteoarthritic cartilage; effect on cartilage metabolism[J]. Osteoarthritis Cartilage, 2007, 15(8) : 872-883.
15. Ku JH, Lee CK, Joo BS, et al. Correlation of synovial fluid leptin concentrations with the severity of osteoarthritis[J]. Clin Rheumatol, 2009, 28(12) : 1431-1435.
16. Koskinen A, Juslin S, Nieminen R, et al. Adiponectin associates with markers of cartilage degradation in osteoarthritis and induces production of proinflammatory and catabolic factors through mitogen-activated protein kinase pathways[J]. Arthritis Res Ther, 2011, 13(6) : R184.
17. Iliopoulos D, Malizos KN, Tsezou A. Epigenetic regulation of leptin affects MMP-13 expression in osteoarthritic chondrocytes: possible molecular target for osteoarthritis therapeutic intervention[J]. Ann Rheum Dis, 2007, 66(12) : 1616-1621.
18. Tong KM, Shieh DC, Chen CP, et al. Leptin induces IL-8 expression via leptin receptor, IRS-1, PI3K, Akt cascade and promotion of NFkappaB/ p300 binding in human synovial fibroblasts[J]. Cell Signal, 2008, 20(8) : 1478-1488.
19. Dumond H, Presle N, Terlain B, et al. Evidence for a key role of leptin in osteoarthritis[J]. Arthritis Rheum, 2003, 48(11) : 3118-3129.
20. Presle N, Pottie P, Dumond H, et al. Differential distribution of adipokines between serum and synovial fluid in patients with osteoarthritis. Contribution of joint tissues to their articular production[J]. Osteoarthrit Cartil, 2006,14(7) : 690-695.

West China Medical Journal

Down-regulated Leptin Receptor by Small Interfering RNA Inhibits the Messenger RNA Expressions of Interleukin-1β and Nitric Oxide of Human Osteoarthritis Chondrocytes

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