EXPRESSION OF Wnt5a IN DORSAL ROOT GANGLIA IN RAT MODEL OF CHRONIC COMPRESSION OF DORSAL ROOT GANGLIA_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

CAOZhenhao ¹ ,  TIANYunhu ² , MALulu ¹ , ZHAOHouling ¹

1. Graduate School of Weifang Medical University, Weifang Shandong, 261042, P. R. China;
2. Department of Spinal Surgery, Affiliated Hospital to Weifang Medical University;

Corresponding author：

TIANYunhu, Email: tianyunhugk@163.com

Keywords：

Dorsal root ganglia; Wnt5a; Chronic compression of dorsal root ganglia model; Radiculopathy; Tumor necrosis factorα; Rat

DOI：

10.7507/1002-1892.20140302

Video：

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Objective To investigate the role of Wnt5a in the mechanism of radiculopathy and the relation between Wnt5a and tumor necrosis factorα(TNF-α) by observing the change of the expression of Wnt5a in the rat model of chronic compression of dorsal root ganglia (CCD). Methods A total of 192 adult male Sprague Dawley rats were allocated into 4 groups: shame group (group A, n=48), CCD group (group B, n=48), CCD+sal ine group (group C, n=48), and CCD+etanercept group (group D, n=48). An L-shaped needle (about 3.5 mm in length, 0.6 mm in diameter) was inserted into the L5 intervertebral foramen, and the dorsal root ganglia (DRG) was compressed by the needle to prepare the CCD model in groups B, C, and D, and then normal sal ine (5.5 mg/kg) or etanercept was injected intraperitoneally in groups C and D. The intervertebral foramen was exposed in group A. The mechanical pain threshold of the posterior paw was tested by the von Frey filaments at 1, 3, 5, and 7 days after operation; the expressions of Wnt5a protein and mRNA were detected at 3 and 7 days after operation by immunohistochemical staining and RT-PCR, respectively. Results The mechanical pain threshold of groups B and C was significantly lower than that of groups A and D, and in group D than in group A (P < 0.05), but no significant difference was found between groups B and C (P > 0.05). The Wnt5a positive cells and the mRNA expression of Wnt5a at 7 days were significantly more than those at 3 days in groups B, C, and D (P < 0.05). The Wnt5a positive cells and the mRNA expression of Wnt5a in groups B and C were significantly more than in groups A and D, and in group D than in group A (P < 0.05), but no significant difference was shown between groups B and C (P > 0.05). Conclusion The expression of Wnt5a in the DRG is increased after CCD. The expression of Wnt5a in the DRG is decreased after the administration of the inhibitor of TNF-α.

Citation： CAOZhenhao, TIANYunhu, MALulu, ZHAOHouling. EXPRESSION OF Wnt5a IN DORSAL ROOT GANGLIA IN RAT MODEL OF CHRONIC COMPRESSION OF DORSAL ROOT GANGLIA. Chinese Journal of Reparative and Reconstructive Surgery, 2014, 28(11): 1392-1396. doi: 10.7507/1002-1892.20140302 Copy

1.	Ohtori S, Suzuki M, Koshi T, et al. Proinflammatory cytokines in the cerebrospinal fluid of patients with lumbar radiculopathy. Eur Spine J, 2011, 20(6):942-946.
2.	Rothman SM, Ma LH, Whiteside GT, et al. Inflammatory cytokine and chemokine expression is differentially modulated acutely in the dorsal root ganglion in response to different nerve root compressions. Spine (Phila Pa 1976), 2011, 36(3):197-202.
3.	Miyoshi S, Sekiguchi M, Konno S, et al. Increased expression of vascular endothelial growth factor protein in dorsal root ganglion exposed to nucleus pulposus on the nerve root in rats. Spine (Phila Pa 1976), 2011, 36(1):E1-6.
4.	Jung YS, Lee HY, Kim SD, et al. Wnt5a stimulates chemotactic migration and chemokine production in human neutrophils. Exp Mol Med, 2013, 45:e27.
5.	Hu SJ, Xing JL. An experimental model for chronic compression of dorsal root ganglion produced by intervertebral foramen stenosis in the rat. Pain, 1998, 77(1):15-23.
6.	Wei H, Zhang Y, Fan ZZ, et al. Effects of colchicine-induced microtubule depolymerization on TRPV4 in rats with chronic compression of the dorsal root ganglion. Neurosci Lett, 2013, 534:344-350.
7.	Malgor R, Bhatt PM, Connolly BA, et al. Wnt5a, TLR2 and TLR4 are elevated in advanced human atherosclerotic lesions. Inflamm Res, 2014, 63(4):277-285.
8.	Lambert C, Dubuc JE, Montell E, et al. Gene expression pattern of cells from inflamed and normal areas of osteoarthritis synovial membrane. Arthritis Rheumatol, 2014, 66(4):960-968.
9.	Bergenfelz C, Medrek C, Ekström E, et al. Wnt5a induces a tolerogenic phenotype of macrophages in sepsis and breast cancer patients. J Immunol, 2012, 188(11):5448-5458.
10.	Sinclair SM, Bhattacharyya J, McDaniel JR, et al. A genetically engineered thermally responsive sustained release curcumin depot to treat neuroinflammation. J Control Release, 2013, 171(1):38-47.
11.	Schroeder M, Viezens L, Schaefer C, et al. Chemokine profile of disc degeneration with acute or chronic pain. J Neurosurg Spine, 2013, 18(5):496-503.
12.	You C, Zhu K, Liu X, et al. Tumor necrosis factor-α-dependent infiltration of macrophages into the dorsal root ganglion in a rat disc herniation model. Spine (Phila Pa 1976), 2013, 38(23):2003-2007.
13.	Di Martino A, Merlini L, Faldini C. Autoimmunity in intervertebral disc herniation:from bench to bedside. Expert Opin Ther Targets, 2013, 17(12):1461-1470.
14.	Shi Y, Yuan S, Li B, et al. Regulation of Wnt signaling by nociceptive input in animal models. Mol Pain, 2012, 8:47.
15.	Li B, Zhong L, Yang X, et al. WNT5A signal ing contributes to Aβ-induced neuroinflammation and neurotoxicity. PLoS One, 2011, 6(8): e22920.
16.	Rauner M, Stein N, Winzer M, et al. WNT5A is induced by inflammatory mediators in bone marrow stromal cells and regulates cytokine and chemokine production. J Bone Miner Res, 2012, 27(3):575-585.
17.	Hiyama A, Yokoyama K, Nukaga T, et al. A complex interaction between Wnt signal ing and TNF-αin nucleus pulposus cells. Arthritis Res Ther, 2013, 15(6):R189.
18.	Briolay A, Lencel P, Bessueille L, et al. Autocrine stimulation of osteoblast activity by Wnt5a in response to TNF-αin human mesenchymal stem cells. Biochem Biophys Res Commun, 2013, 430(3):1072-1077.
19.	Allen KD, Shamji MF, Mata BA, et al. Kinematic and dynamic gait compensations in a rat model of lumbar radiculopathy and the effects of tumor necrosis factor-alpha antagonism. Arthritis Res Ther, 2011, 13(4):R137.
20.	Fava RA, Olsen NJ, Spencer-Green G, et al. Vascular permeability factor/ endothelial growth factor (VPF/VEGF):accumulation and expression in human synovial fluids and rheumatoid synovial tissue. J Exp Med, 1994, 180(1):341-346.

1. Ohtori S, Suzuki M, Koshi T, et al. Proinflammatory cytokines in the cerebrospinal fluid of patients with lumbar radiculopathy. Eur Spine J, 2011, 20(6):942-946.
2. Rothman SM, Ma LH, Whiteside GT, et al. Inflammatory cytokine and chemokine expression is differentially modulated acutely in the dorsal root ganglion in response to different nerve root compressions. Spine (Phila Pa 1976), 2011, 36(3):197-202.
3. Miyoshi S, Sekiguchi M, Konno S, et al. Increased expression of vascular endothelial growth factor protein in dorsal root ganglion exposed to nucleus pulposus on the nerve root in rats. Spine (Phila Pa 1976), 2011, 36(1):E1-6.
4. Jung YS, Lee HY, Kim SD, et al. Wnt5a stimulates chemotactic migration and chemokine production in human neutrophils. Exp Mol Med, 2013, 45:e27.
5. Hu SJ, Xing JL. An experimental model for chronic compression of dorsal root ganglion produced by intervertebral foramen stenosis in the rat. Pain, 1998, 77(1):15-23.
6. Wei H, Zhang Y, Fan ZZ, et al. Effects of colchicine-induced microtubule depolymerization on TRPV4 in rats with chronic compression of the dorsal root ganglion. Neurosci Lett, 2013, 534:344-350.
7. Malgor R, Bhatt PM, Connolly BA, et al. Wnt5a, TLR2 and TLR4 are elevated in advanced human atherosclerotic lesions. Inflamm Res, 2014, 63(4):277-285.
8. Lambert C, Dubuc JE, Montell E, et al. Gene expression pattern of cells from inflamed and normal areas of osteoarthritis synovial membrane. Arthritis Rheumatol, 2014, 66(4):960-968.
9. Bergenfelz C, Medrek C, Ekström E, et al. Wnt5a induces a tolerogenic phenotype of macrophages in sepsis and breast cancer patients. J Immunol, 2012, 188(11):5448-5458.
10. Sinclair SM, Bhattacharyya J, McDaniel JR, et al. A genetically engineered thermally responsive sustained release curcumin depot to treat neuroinflammation. J Control Release, 2013, 171(1):38-47.
11. Schroeder M, Viezens L, Schaefer C, et al. Chemokine profile of disc degeneration with acute or chronic pain. J Neurosurg Spine, 2013, 18(5):496-503.
12. You C, Zhu K, Liu X, et al. Tumor necrosis factor-α-dependent infiltration of macrophages into the dorsal root ganglion in a rat disc herniation model. Spine (Phila Pa 1976), 2013, 38(23):2003-2007.
13. Di Martino A, Merlini L, Faldini C. Autoimmunity in intervertebral disc herniation:from bench to bedside. Expert Opin Ther Targets, 2013, 17(12):1461-1470.
14. Shi Y, Yuan S, Li B, et al. Regulation of Wnt signaling by nociceptive input in animal models. Mol Pain, 2012, 8:47.
15. Li B, Zhong L, Yang X, et al. WNT5A signal ing contributes to Aβ-induced neuroinflammation and neurotoxicity. PLoS One, 2011, 6(8): e22920.
16. Rauner M, Stein N, Winzer M, et al. WNT5A is induced by inflammatory mediators in bone marrow stromal cells and regulates cytokine and chemokine production. J Bone Miner Res, 2012, 27(3):575-585.
17. Hiyama A, Yokoyama K, Nukaga T, et al. A complex interaction between Wnt signal ing and TNF-αin nucleus pulposus cells. Arthritis Res Ther, 2013, 15(6):R189.
18. Briolay A, Lencel P, Bessueille L, et al. Autocrine stimulation of osteoblast activity by Wnt5a in response to TNF-αin human mesenchymal stem cells. Biochem Biophys Res Commun, 2013, 430(3):1072-1077.
19. Allen KD, Shamji MF, Mata BA, et al. Kinematic and dynamic gait compensations in a rat model of lumbar radiculopathy and the effects of tumor necrosis factor-alpha antagonism. Arthritis Res Ther, 2011, 13(4):R137.
20. Fava RA, Olsen NJ, Spencer-Green G, et al. Vascular permeability factor/ endothelial growth factor (VPF/VEGF):accumulation and expression in human synovial fluids and rheumatoid synovial tissue. J Exp Med, 1994, 180(1):341-346.

Chinese Journal of Reparative and Reconstructive Surgery

EXPRESSION OF Wnt5a IN DORSAL ROOT GANGLIA IN RAT MODEL OF CHRONIC COMPRESSION OF DORSAL ROOT GANGLIA

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