SIGNIFICANCE OF CXCL-13 GENE EXPRESSION IN KNEE OSTEOARTHRITIS SYNOVIUM_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

 RENHongge , LIZhenhao , LIGuozhen , JINJingri

No.1 Department of Orthopedics, Yanbian University Hospital, Yanji Jilin, 133000, P. R. China;

Corresponding author：

RENHongge, Email: renhg196@sina.com

Keywords：

Osteoarthritis; CXCL13; Synovium

DOI：

10.7507/1002-1892.20150010

Video：

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Objective To investigate the role of CXCL13 in the onset and development of knee osteoarthritis by observing and comparing the expression of CXCL13 between osteoarthritis and normal synovium. Methods The synovium samples were collected from 30 patients with osteoarthritis who received total knee replacement (osteoarthritis group), including 11 males and 19 females with an average age of 66.7 years (range, 62-76 years). The synovium samples were collected from 22 patients without osteoarthritis who underwent traumatic amputation (control group), including 15 males and 7 females with an average age of 51.3 years (range, 48-56 years). The NimbleGen microarray detection was used to defect differentially expressed genes; the immunohistochemistry staining, Western blot, and real-time quantitative PCR (qRT-PCR) were used to detect the expressions of CXCL13 mRNA and protein. Results There were 451 up-regulated genes and 810 down-regulated genes in the 22 885 genes which contained by mRNA gene chip, and CXCL13 gene expression was down-regulated. Immunohistochemistry staining and Western blot assay showed that the expression of CXCL13 protein was significantly lower in osteoarthritis group (0.408 0±0.101 8) than in control group (0.785 9±0.057 9) (t=15.630, P=0.000). qRT-PCR results showed that the expression of CXCL13 mRNA was significantly lower in osteoarthritis group (0.011 7±0.003 2) than in control group (1.041 4±0.129 7) (t=43.634, P=0.000). Conclusion Low expression of CXCL13 in the knee osteoarthritis synovium tissue may be associated with the onset and development of knee osteoarthritis.

Citation： RENHongge, LIZhenhao, LIGuozhen, JINJingri. SIGNIFICANCE OF CXCL-13 GENE EXPRESSION IN KNEE OSTEOARTHRITIS SYNOVIUM. Chinese Journal of Reparative and Reconstructive Surgery, 2015, 29(1): 39-42. doi: 10.7507/1002-1892.20150010 Copy

1.	Blagojevic M, Jinks C, Jeffery A, et al. Risk factors for onset of osteoarthritis of the knee in older adults:a systematic review and meta-analysis. Osteoarthritis Cartilage, 2010, 18(1):24-33.
2.	Gerard C, Rollins BJ. Chemokines and disease. Nat Immunol, 2001, 2(2):108-115.
3.	Braunersreuther V, Viviani GL, Mach F, et al. Role of cytokines and chemokines in non-alcoholic fatty liver disease. World J Gastroenterol, 2012, 18(8):727-735.
4.	Bugatti S, Manzo A, Vitolo B, et al. High expression levels of the B cell chemoattractant CXCL13 in rheumatoid synovium are a marker of severe disease. Rheumatology (Oxford), 2014, 53(10):1886-1895.
5.	Greisen S, Schelde K, Rasmussen T, et al. CXCL13 predicts disease activity in early rheumatoid arthritis and could be an indicator of the therapeutic window of opportunity. Arthritis Res Ther, 2014, 16(5):434.
6.	Jones JD, Hamilton BJ, Challener GJ, et al. Serum C-X-C motif chemokine 13 is elevated in early and established rheumatoid arthritis and correlates with rheumatoid factor levels. Arthritis Res Ther, 2014, 16(2):R103.
7.	Platas J, Guillén MI, Del Caz MD, et al. Conditioned media from adipose-tissue-derived mesenchymal stem cells downregulate degradative mediators induced by interleukin-1β in osteoarthritic chondrocytes. Mediators Inflamm, 2013:354014.
8.	Liu C, Weng YG, Yuan TX, et al. CXCL12/CXCR4 signal axis plays an important role in mediating bone morphogenetic protein 9-induced osteogenic differentiation of mesenchymal stem cells. Int J Med Sci, 2013, 10(9):1181-1192.
9.	Forestier R, Francon A, Briole V, et al. Prevalence of generalized osteoarthritis in a population with knee osteoarthritis. Joint Bone Spine, 2011, 78(3):275-278.
10.	Yamairi F, Utsumi H, Ono Y, et al. Expression of vascular endothelial growth factor (VEGF) associated with histopathological changes in rodent models of osteoarthritis. J Toxicol Pathol, 2011, 24(2):137-142.
11.	Sartori-Cintra AR, Mara CS, Argolo DL, et al. Regulation of hypoxia-inducible factor-1a(HIF-1α)expression by interleukin-1β(IL-1β), insulin-like growth factors I (IGF-I) and Ⅱ (IGF-Ⅱ) in human osteoarthritic chondrocytes. Clinics (Sao Paulo), 2012, 67(1):35-40.
12.	Nagahara M, Waguri-Nagaya Y, Yamagami T, et al. TNF-alphainduced aquaporin 9 in synoviocytes from patients with OA and RA. Rheumatology (Oxford), 2010, 49(5):898-906.
13.	李敏, 梁翼, 吴晓惠, 等. 伴骨髓水肿的膝骨关节炎患者白细胞介素-1β白细胞介素-6肿瘤坏死因子-α的相关性研究. 中华风湿病杂志, 2012, 16(2):107-110.
14.	徐焕宾, 熊思东. 新发现的CXCL16趋化因子及其受体. 生命的化学, 2003, 23(1):8-10.
15.	Wojdasiewicz P, Poniatowski LA, Kotela A, et al. The chemokine CX3CL1(fractalkine) and its receptor CX3CR1:occurrence and potential role in osteoarthritis. Arch Immunol Ther Exp (Warsz), 2014, 62(5):395-403.
16.	Shen W, Chen J, Zhu T, et al. Intra-articular injection of human meniscus stem/progenitor cells promotes meniscus regeneration and ameliorates osteoarthritis through stromal cell-derived factor-1/CXCR4-mediated homing. Stem Cells Transl Med, 2014, 3(3):387-394.
17.	Kowarik MC, Cepok S, Sellner J, et al. CXCL13 is the major determinant for B cell recruitment to the CSF during neuroinflammation. J Neuroinflammation, 2012, 9:93-104.
18.	Silva JS, Andrade AC, Santana CC, et al. Low CXCL13 expression, splenic lymphoid tissue atrophy and germinal center disruption in severe canine visceral leishmaniasis. PLoS One, 2012, 7(1):e29103-29113.
19.	Kobayashi S, Murata K, Shibuya H, et al. A distinct human CD4⁺ T cell subset that secretes CXCL13 in rheumatoid synovium. Arthritis Rheum, 2013, 65(12):3063-3072.
20.	Halvorsen B, Smedbakken LM, Michelsen AE, et al. Activated platelets promote increased monocyte expression of CXCR5 through prostaglandin E2-related mechanisms and enhance the anti-inflammatory effects of CXCL13. Atherosclerosis, 2014, 234(2):352-359.
21.	Yuvaraj S, Griffin AC, Sundaram K, et al. A novel function of CXCL13 to stimulate RANK ligand expression in oral squamous cell carcinoma cells. Mol Cancer Res, 2009, 7(8):1399-1407.
22.	Sambandam Y, Sundaram K, Liu A, et al. CXCL13 activation of c-Myc induces RANK ligand expression in stromal/preosteoblast cells in the oral squamous cell carcinoma tumor-bone microenvironment. Oncogene, 2013, 32(1):97-105.

1. Blagojevic M, Jinks C, Jeffery A, et al. Risk factors for onset of osteoarthritis of the knee in older adults:a systematic review and meta-analysis. Osteoarthritis Cartilage, 2010, 18(1):24-33.
2. Gerard C, Rollins BJ. Chemokines and disease. Nat Immunol, 2001, 2(2):108-115.
3. Braunersreuther V, Viviani GL, Mach F, et al. Role of cytokines and chemokines in non-alcoholic fatty liver disease. World J Gastroenterol, 2012, 18(8):727-735.
4. Bugatti S, Manzo A, Vitolo B, et al. High expression levels of the B cell chemoattractant CXCL13 in rheumatoid synovium are a marker of severe disease. Rheumatology (Oxford), 2014, 53(10):1886-1895.
5. Greisen S, Schelde K, Rasmussen T, et al. CXCL13 predicts disease activity in early rheumatoid arthritis and could be an indicator of the therapeutic window of opportunity. Arthritis Res Ther, 2014, 16(5):434.
6. Jones JD, Hamilton BJ, Challener GJ, et al. Serum C-X-C motif chemokine 13 is elevated in early and established rheumatoid arthritis and correlates with rheumatoid factor levels. Arthritis Res Ther, 2014, 16(2):R103.
7. Platas J, Guillén MI, Del Caz MD, et al. Conditioned media from adipose-tissue-derived mesenchymal stem cells downregulate degradative mediators induced by interleukin-1β in osteoarthritic chondrocytes. Mediators Inflamm, 2013:354014.
8. Liu C, Weng YG, Yuan TX, et al. CXCL12/CXCR4 signal axis plays an important role in mediating bone morphogenetic protein 9-induced osteogenic differentiation of mesenchymal stem cells. Int J Med Sci, 2013, 10(9):1181-1192.
9. Forestier R, Francon A, Briole V, et al. Prevalence of generalized osteoarthritis in a population with knee osteoarthritis. Joint Bone Spine, 2011, 78(3):275-278.
10. Yamairi F, Utsumi H, Ono Y, et al. Expression of vascular endothelial growth factor (VEGF) associated with histopathological changes in rodent models of osteoarthritis. J Toxicol Pathol, 2011, 24(2):137-142.
11. Sartori-Cintra AR, Mara CS, Argolo DL, et al. Regulation of hypoxia-inducible factor-1a(HIF-1α)expression by interleukin-1β(IL-1β), insulin-like growth factors I (IGF-I) and Ⅱ (IGF-Ⅱ) in human osteoarthritic chondrocytes. Clinics (Sao Paulo), 2012, 67(1):35-40.
12. Nagahara M, Waguri-Nagaya Y, Yamagami T, et al. TNF-alphainduced aquaporin 9 in synoviocytes from patients with OA and RA. Rheumatology (Oxford), 2010, 49(5):898-906.
13. 李敏, 梁翼, 吴晓惠, 等. 伴骨髓水肿的膝骨关节炎患者白细胞介素-1β白细胞介素-6肿瘤坏死因子-α的相关性研究. 中华风湿病杂志, 2012, 16(2):107-110.
14. 徐焕宾, 熊思东. 新发现的CXCL16趋化因子及其受体. 生命的化学, 2003, 23(1):8-10.
15. Wojdasiewicz P, Poniatowski LA, Kotela A, et al. The chemokine CX3CL1(fractalkine) and its receptor CX3CR1:occurrence and potential role in osteoarthritis. Arch Immunol Ther Exp (Warsz), 2014, 62(5):395-403.
16. Shen W, Chen J, Zhu T, et al. Intra-articular injection of human meniscus stem/progenitor cells promotes meniscus regeneration and ameliorates osteoarthritis through stromal cell-derived factor-1/CXCR4-mediated homing. Stem Cells Transl Med, 2014, 3(3):387-394.
17. Kowarik MC, Cepok S, Sellner J, et al. CXCL13 is the major determinant for B cell recruitment to the CSF during neuroinflammation. J Neuroinflammation, 2012, 9:93-104.
18. Silva JS, Andrade AC, Santana CC, et al. Low CXCL13 expression, splenic lymphoid tissue atrophy and germinal center disruption in severe canine visceral leishmaniasis. PLoS One, 2012, 7(1):e29103-29113.
19. Kobayashi S, Murata K, Shibuya H, et al. A distinct human CD4⁺ T cell subset that secretes CXCL13 in rheumatoid synovium. Arthritis Rheum, 2013, 65(12):3063-3072.
20. Halvorsen B, Smedbakken LM, Michelsen AE, et al. Activated platelets promote increased monocyte expression of CXCR5 through prostaglandin E2-related mechanisms and enhance the anti-inflammatory effects of CXCL13. Atherosclerosis, 2014, 234(2):352-359.
21. Yuvaraj S, Griffin AC, Sundaram K, et al. A novel function of CXCL13 to stimulate RANK ligand expression in oral squamous cell carcinoma cells. Mol Cancer Res, 2009, 7(8):1399-1407.
22. Sambandam Y, Sundaram K, Liu A, et al. CXCL13 activation of c-Myc induces RANK ligand expression in stromal/preosteoblast cells in the oral squamous cell carcinoma tumor-bone microenvironment. Oncogene, 2013, 32(1):97-105.

Chinese Journal of Reparative and Reconstructive Surgery

SIGNIFICANCE OF CXCL-13 GENE EXPRESSION IN KNEE OSTEOARTHRITIS SYNOVIUM

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