Effect of autotaxin-lysophosphatidic acid pathway on matrix metalloproteinase-13 in articular cartilage of knee osteoarthritis in rats_West China Medical Journal

Authors：

LI Xue ,  ZHANG Changjie

Department of Rehabilitation, the Second Xiangya Hospital of Central South University, Changsha, Hunan 410000, P. R. China;

Corresponding author：

ZHANG Changjie, Email: zcj3483@126.com

Keywords：

Autotaxin; Lysophosphatidic acid; Osteoarthritis; Cartilage; Rat

DOI：

10.7507/1002-0179.202003505

Video：

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Objective To investigate the effect of inhibiting autotaxin (ATX)-lysophosphatidic acid (LPA) pathway on the cartilage of knee osteoarthritis in rats.Methods Primary chondrocytes within three generations of Sprague-Dawley rats (8 weeks old, male) were randomly divided into 6 groups, including blank control group, model group, 1 μmol/L PF-8380 group, 10 μmol/L PF-8380 group, 1 μmol/L Ki16425 group, and 10 μmol/L Ki16425 group. Except for the blank control group, the other groups were modeled with osteoarthritis using interleukin-1β (10 ng/mL, 24 h), and then the experimental groups, i.e., 1 μmol/L PF-8380 group, 10 μmol/L PF-8380 group, 1 μmol/L Ki16425 group, and 10 μmol/L Ki16425 group, were intervened with 1, 10 μmol/L PF-8380 (ATX inhibitor) and 1, 10 μmol/L Ki16425 (LPA receptor antagonist) for 24 h, respectively. immunocytochemistry staining was used to determine the expression of type Ⅱ collagen (Col Ⅱ) in cytoplasm, and Western Blot was used to determine the expression of ATX, LPA, and matrix metalloproteinase-13 (MMP-13) in chondrocytes.Results Compared with the blank control group, the average absorbance of Col Ⅱ in chondrocytes in the model group was significantly reduced (0.003 9±0.000 8 vs. 0.110 0± 0.009 0, P<0.05). The expression levels of ATX, LPA, and MMP-13 in chondrocytes in the model group, 1 μmol/L PF-8380 group, 10 μmol/L PF-8380 group, and 1 μmol/L Ki16425 group were significantly higher than those in the blank control group, while the expression levels of ATX, LPA, and MMP-13 in the 10 μmol/L Ki16425 group had no significant difference with those in the blank control group; the expression levels of ATX, LPA, and MMP-13 in the model group, 10 μmol/L PF-8380 group, and 1 μmol/L PF-8380 group decreased in order; the expression levels of ATX, LPA, and MMP-13 in the model group, 1 μmol/L Ki16425 group, and 10 μmol/L Ki16425 group decreased in order.Conclusion Inhibiting ATX-LPA pathway may inhibit the up-regulation of MMP-13 levels in articular cartilage of osteoarthritis in rats to reduce the damage of cartilage.

Citation： LI Xue, ZHANG Changjie. Effect of autotaxin-lysophosphatidic acid pathway on matrix metalloproteinase-13 in articular cartilage of knee osteoarthritis in rats. West China Medical Journal, 2020, 35(5): 550-554. doi: 10.7507/1002-0179.202003505 Copy

1.	Sulzbacher I. Osteoarthritis: histology and pathogenesis. Wien Med Wochenschr, 2013, 163(9/10): 212-219.
2.	Scanzello CR, Goldring SR. The role of synovitis in osteoarthritis pathogenesis. Bone, 2012, 51(2, SI): 249-257.
3.	Giganti A, Rodriguez M, Fould B, et al. Murine and human autotaxin alpha, beta, and gamma isoforms: gene organization, tissue distribution, and biochemical characterization. J Biol Chem, 2008, 283(12): 7776-7789.
4.	Umezu-Goto M, Kishi Y, Taira A, et al. Autotaxin has lysophospholipase D activity leading to tumor cell growth and motility by lysophosphatidic acid production. J Cell Biol, 2002, 158(2): 227-233.
5.	Moolenaar WH, Hla T. SnapShot: bioactive lysophospholipids. Cell, 2012, 148(1/2): 378-378.e2.
6.	Aikawa S, Hashimoto T, Kano K, et al. Lysophosphatidic acid as a lipid mediator with multiple biological actions. J Biochem, 2015, 157(2): 81-89.
7.	Benesch MG, Tang X, Venkatraman G, et al. Recent advances in targeting the autotaxin-lysophosphatidate-lipid phosphate phosphatase axis in vivo. J Biomed Res, 2016, 30: 272-284.
8.	Sevastou I, Kaffe E, Marios-Angelos M, et al. Lysoglycerophospholipids in chronic inflammatory disorders: The PLA2/LPC and ATX/LPA axes. Biochim Biophys Acta, 2013, 1831(1): 42-60.
9.	Blackburn J, Mansell JP. The emerging role of lysophosphatidic acid (LPA) in skeletal biology. Bone, 2012, 50(3): 756-762.
10.	Arden N, Nevitt MC. Osteoarthritis: epidemiology. Best Pract Res Clin Rheumatol, 2006, 20(1): 3-25.
11.	Laufer S. Osteoarthritis therapy--are there still unmet needs?. Rheumatology, 2004, 43(91): i9-i15.
12.	Magkrioti C, Galaris A, Kanellopoulou P, et al. Autotaxin and chronic inflammatory diseases. J Autoimmun, 2019, 104: 102327.
13.	Gierse J, Thorarensen A, Beltey K, et al. A novel autotaxin inhibitor reduces lysophosphatidic acid levels in plasma and the site of inflammation. J Pharmacol Exp Ther, 2010, 334(1): 310-317.
14.	Mabey T, Taleongpong P, Udomsinprasert W, et al. Plasma and synovial fluid autotaxin correlate with severity in knee osteoarthritis. Clin Chim Acta, 2015, 444: 72-77.
15.	Nikitopoulou I, Oikonomou N, Karouzakis E, et al. Autotaxin expression from synovial fibroblasts is essential for the pathogenesis of modeled arthritis. J Exp Med, 2012, 209(5): 925-933.
16.	Cooper AB, Wu J, Lu D, et al. Is autotaxin (ENPP2) the Link between hepatitis C and hepatocellular cancer?. J Gastrointest Surg, 2007, 11(12): 1628-1635.
17.	Zhao CQ, Fernandes MJ, Prestwich GD, et al. Regulation of lysophosphatidic acid receptor expression and function in human synoviocytes: implications for rheumatoid arthritis?. Mol Pharmacol, 2008, 73(2): 587-600.
18.	McDougall JJ, Albacete S, Schuelert N, et al. Lysophosphatidic acid provides a missing link between osteoarthritis and joint neuropathic pain. Osteoarthritis Cartilage, 2017, 25(6): 926-934.
19.	Zhang HL, Xu XY, Gajewiak J, et al. Dual activity lysophosphatidic acid receptor pan-antagonist/autotaxin inhibitor reduces breast cancer cell migration in vitro and causes tumor regression in vivo. Cancer Res, 2009, 69(13): 5441-5449.
20.	Miyabe Y, Miyabe C, Iwai Y, et al. Necessity of lysophosphatidic acid receptor 1 for development of arthritis. Arthritis Rheum, 2013, 65(8): 2037-2047.
21.	Choi JW, Lee CW, Chun J. Biological roles of lysophospholipid receptors revealed by genetic null mice: an update. Biochim Biophys Acta, 2008, 1781(9): 531-539.
22.	Shen P, Tu S, Wang H, et al. Simiao pill attenuates collagen-induced arthritis in rats through suppressing the ATX-LPA and MAPK signalling pathways. Evid Based Complement Alternat Med, 2019, 2019: 1-11.

1. Sulzbacher I. Osteoarthritis: histology and pathogenesis. Wien Med Wochenschr, 2013, 163(9/10): 212-219.
2. Scanzello CR, Goldring SR. The role of synovitis in osteoarthritis pathogenesis. Bone, 2012, 51(2, SI): 249-257.
3. Giganti A, Rodriguez M, Fould B, et al. Murine and human autotaxin alpha, beta, and gamma isoforms: gene organization, tissue distribution, and biochemical characterization. J Biol Chem, 2008, 283(12): 7776-7789.
4. Umezu-Goto M, Kishi Y, Taira A, et al. Autotaxin has lysophospholipase D activity leading to tumor cell growth and motility by lysophosphatidic acid production. J Cell Biol, 2002, 158(2): 227-233.
5. Moolenaar WH, Hla T. SnapShot: bioactive lysophospholipids. Cell, 2012, 148(1/2): 378-378.e2.
6. Aikawa S, Hashimoto T, Kano K, et al. Lysophosphatidic acid as a lipid mediator with multiple biological actions. J Biochem, 2015, 157(2): 81-89.
7. Benesch MG, Tang X, Venkatraman G, et al. Recent advances in targeting the autotaxin-lysophosphatidate-lipid phosphate phosphatase axis in vivo. J Biomed Res, 2016, 30: 272-284.
8. Sevastou I, Kaffe E, Marios-Angelos M, et al. Lysoglycerophospholipids in chronic inflammatory disorders: The PLA2/LPC and ATX/LPA axes. Biochim Biophys Acta, 2013, 1831(1): 42-60.
9. Blackburn J, Mansell JP. The emerging role of lysophosphatidic acid (LPA) in skeletal biology. Bone, 2012, 50(3): 756-762.
10. Arden N, Nevitt MC. Osteoarthritis: epidemiology. Best Pract Res Clin Rheumatol, 2006, 20(1): 3-25.
11. Laufer S. Osteoarthritis therapy--are there still unmet needs?. Rheumatology, 2004, 43(91): i9-i15.
12. Magkrioti C, Galaris A, Kanellopoulou P, et al. Autotaxin and chronic inflammatory diseases. J Autoimmun, 2019, 104: 102327.
13. Gierse J, Thorarensen A, Beltey K, et al. A novel autotaxin inhibitor reduces lysophosphatidic acid levels in plasma and the site of inflammation. J Pharmacol Exp Ther, 2010, 334(1): 310-317.
14. Mabey T, Taleongpong P, Udomsinprasert W, et al. Plasma and synovial fluid autotaxin correlate with severity in knee osteoarthritis. Clin Chim Acta, 2015, 444: 72-77.
15. Nikitopoulou I, Oikonomou N, Karouzakis E, et al. Autotaxin expression from synovial fibroblasts is essential for the pathogenesis of modeled arthritis. J Exp Med, 2012, 209(5): 925-933.
16. Cooper AB, Wu J, Lu D, et al. Is autotaxin (ENPP2) the Link between hepatitis C and hepatocellular cancer?. J Gastrointest Surg, 2007, 11(12): 1628-1635.
17. Zhao CQ, Fernandes MJ, Prestwich GD, et al. Regulation of lysophosphatidic acid receptor expression and function in human synoviocytes: implications for rheumatoid arthritis?. Mol Pharmacol, 2008, 73(2): 587-600.
18. McDougall JJ, Albacete S, Schuelert N, et al. Lysophosphatidic acid provides a missing link between osteoarthritis and joint neuropathic pain. Osteoarthritis Cartilage, 2017, 25(6): 926-934.
19. Zhang HL, Xu XY, Gajewiak J, et al. Dual activity lysophosphatidic acid receptor pan-antagonist/autotaxin inhibitor reduces breast cancer cell migration in vitro and causes tumor regression in vivo. Cancer Res, 2009, 69(13): 5441-5449.
20. Miyabe Y, Miyabe C, Iwai Y, et al. Necessity of lysophosphatidic acid receptor 1 for development of arthritis. Arthritis Rheum, 2013, 65(8): 2037-2047.
21. Choi JW, Lee CW, Chun J. Biological roles of lysophospholipid receptors revealed by genetic null mice: an update. Biochim Biophys Acta, 2008, 1781(9): 531-539.
22. Shen P, Tu S, Wang H, et al. Simiao pill attenuates collagen-induced arthritis in rats through suppressing the ATX-LPA and MAPK signalling pathways. Evid Based Complement Alternat Med, 2019, 2019: 1-11.

West China Medical Journal

Effect of autotaxin-lysophosphatidic acid pathway on matrix metalloproteinase-13 in articular cartilage of knee osteoarthritis in rats

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