Expressions of Renin, angiotensin converting enzyme, angiotensin receptor 1, and angiotensin receptor 2 in synovial tissue of osteoarthritis at different stages_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

WU Yuangang , ZENG Yi , LI Mingyang , LIU Yuan , YANG Jing ,  SHEN Bin

Department of Orthopedics, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P.R.China;

Corresponding author：

SHEN Bin, Email: shenbin_1971@ 163.com

Keywords：

Osteoarthritis; synovial tissue; Renin; angiotensin converting enzyme; angiotensin receptor

DOI：

10.7507/1002-1892.201904065

Video：

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Objective To study the expressions of Renin, angiotensin converting enzyme (ACE), angiotensin receptor 1 (AT1R), and AT2R in synovial tissue of osteoarthritis (OA) at different stages.Methods The patients who were treated with upper knee amputation because of trauma or total knee arthroplasty for OA between January 2018 and December 2018 were enrolled. Among them, 32 patients who met the selection criteria were included in the study. According to the Kellgren-Lawrence (K-L) X-ray classification, they were allocated to normal synovial group (group A, n=9), moderate OA synovial group (group B, n=11, K-L level 3), and advanced OA synovial group (group C, n=12, K-L level 4). The relative expressions of Renin, ACE, AT1R, and AT2R mRNAs and proteins were detected by real-time fluorescence quantitative PCR (qRT-PCR) and Western blot.Results The relative expressions of Renin, ACE, and AT1R mRNAs and proteins were significantly higher in group B and group C than in group A (P<0.05). The relative expressions of ACE and AT1R mRNAs and proteins and Renin protein were significantly higher in group C than in group B (P<0.05). However, the relative expressions of AT2R mRNA and protein were lower in group B and group C than in group A (P<0.05), and in group C than in group B (P<0.05).Conclusion The expressions of Renin, ACE, and AT1R in synovial tissue of osteoarthritis significantly increase as the K-L level increased, and the expression of AT2R decreases. Renin, ACE, AT1R, and AT2R have a certain degree of correlation with the development of OA.

Citation： WU Yuangang, ZENG Yi, LI Mingyang, LIU Yuan, YANG Jing, SHEN Bin. Expressions of Renin, angiotensin converting enzyme, angiotensin receptor 1, and angiotensin receptor 2 in synovial tissue of osteoarthritis at different stages. Chinese Journal of Reparative and Reconstructive Surgery, 2020, 34(3): 362-366. doi: 10.7507/1002-1892.201904065 Copy

1.	Jiang Y, Tuan RS. Origin and function of cartilage stem/progenitor cells in osteoarthritis. Nat Rev Rheumatol, 2015, 11(4): 206-212.
2.	陈闻波, 蔡江瑜, 孙亚英, 等. 应用干细胞旁分泌效应治疗膝部骨关节炎的研究进展. 中国修复重建外科杂志, 2019, 33(11): 1446-1451.
3.	Zhang W, Zhang C, Luo C, et al. Design, cyclization, and optimization of MMP13-TIMP1 interaction-derived self-inhibitory peptides against chondrocyte senescence in osteoarthritis. Int J Biol Macromol, 2019, 121: 921-929.
4.	Alvarez A, Cerdá-Nicolás M, Naim Abu Nabah Y, et al. Direct evidence of leukocyte adhesion in arterioles by angiotensin Ⅱ. Blood, 2004, 104(2): 402-408.
5.	张加强, 魏长征, 吴祎, 等. 交联几丁糖治疗兔膝骨关节炎的实验研究. 中国修复重建外科杂志, 2019, 33(2): 185-189.
6.	Han C, Liu J, Liu X, et al. Angiotensin Ⅱ induces C-reactive protein expression through ERK1/2 and JNK signaling in human aortic endothelial cells. Atherosclerosis, 2010, 212(1): 206-212.
7.	Brzozowski T. Role of renin-angiotensin system and metabolites of angiotensin in the mechanism of gastric mucosal protection. Curr Opin Pharmacol, 2014, 19: 90-98.
8.	Das UN. Angiotensin-Ⅱbehaves as an endogenous pro-inflammatory molecule. J Assoc Physicians India, 2005, 53: 472-476.
9.	Zhang FY, Yang FJ, Yang JL, et al. Renin inhibition improves ovariectomy-induced osteoporosis of lumbar vertebra in mice. Biol Pharm Bull, 2014, 37(12): 1994-1997.
10.	Byon IS, Lee DH, Jun ES, et al. Effect of angiotensin Ⅱ type 1 receptor blocker and angiotensin converting enzyme inhibitor on the intraocular growth factors and their receptors in streptozotocin-induced diabetic rats. Int J Ophthalmol, 2017, 10(6): 896-901.
11.	Wu Y, Lu X, Li M, et al. Renin-angiotensin system in osteoarthritis: A new potential therapy. Int Immunopharmacol, 2019, 75: 105796.
12.	Caspritz G, Alpermann HG, Schleyerbach R. Influence of the new angiotensin converting enzyme inhibitor ramipril on several models of acute inflammation and the adjuvant arthritis in the rat. Arzneimittelforschung, 1986, 36(11): 1605-1608.
13.	Wang Y, Kou J, Zhang H, et al. The renin-angiotensin system in the synovium promotes periarticular osteopenia in a rat model of collagen-induced arthritis. Int Immunopharmacol, 2018, 65: 550-558.
14.	Kohn MD, Sassoon AA, Fernando ND. Classifications in brief: Kellgren-Lawrence classification of osteoarthritis. Clin Orthop Relat Res, 2016, 474(8): 1886-1893.
15.	Goldring SR. Alterations in periarticular bone and cross talk between subchondral bone and articular cartilage in osteoarthritis. Ther Adv Musculoskelet Dis, 2012, 4(4): 249-255.
16.	Kawakami Y, Matsuo K, Murata M, et al. Expression of angiotensin Ⅱ receptor-1 in human articular chondrocytes. Arthritis, 2012, 2012: 648537.
17.	Tsukamoto I, Akagi M, Inoue S, et al. Expression of local renin-angiotensin system components in chondrocytes. Eur J Histochem, 2014, 58(2): 2387.
18.	Kawahata H, Sotobayashi D, Aoki M, et al. Continuous infusion of angiotensin Ⅱ modulates hypertrophic differentiation and apoptosis of chondrocytes in cartilage formation in a fracture model mouse. Hypertens Res, 2015, 38(6): 382-393.
19.	Martin MF, Surrall KE, McKenna F, et al. Captopril: a new treatment for rheumatoid arthritis? Lancet, 1984, 1(8390): 1325-1328.
20.	Walsh DA, Suzuki T, Knock GA, et al. AT1 receptor characteristics of angiotensin analogue binding in human synovium. Br J Pharmacol, 1994, 112(2): 435-442.
21.	Silveira KD, Coelho FM, Vieira AT, et al. Mechanisms of the anti-inflammatory actions of the angiotensin type 1 receptor antagonist losartan in experimental models of arthritis. Peptides, 2013, 46: 53-63.
22.	Kaschina E, Unger T. Angiotensin AT1/AT2 receptors: regulation, signalling and function. Blood Press, 2003, 12(2): 70-88.
23.	Scott BB, Zaratin PF, Gilmartin AG, et al. TNF-alpha modulates angiopoietin-1 expression in rheumatoid synovial fibroblasts via the NF-kappa B signalling pathway. Biochem Biophys Res Commun, 2005, 328(2): 409-414.
24.	Tang Y, Hu X, Lu X. Captopril, an angiotensin-converting enzyme inhibitor, possesses chondroprotective efficacy in a rat model of osteoarthritis through suppression local renin-angiotensin system. Int J Clin Exp Med, 2015, 8(8): 12584-12592.
25.	Sagawa K, Nagatani K, Komagata Y, et al. Angiotensin receptor blockers suppress antigen-specific T cell responses and ameliorate collagen-induced arthritis in mice. Arthritis Rheum, 2005, 52(6): 1920-1928.

1. Jiang Y, Tuan RS. Origin and function of cartilage stem/progenitor cells in osteoarthritis. Nat Rev Rheumatol, 2015, 11(4): 206-212.
2. 陈闻波, 蔡江瑜, 孙亚英, 等. 应用干细胞旁分泌效应治疗膝部骨关节炎的研究进展. 中国修复重建外科杂志, 2019, 33(11): 1446-1451.
3. Zhang W, Zhang C, Luo C, et al. Design, cyclization, and optimization of MMP13-TIMP1 interaction-derived self-inhibitory peptides against chondrocyte senescence in osteoarthritis. Int J Biol Macromol, 2019, 121: 921-929.
4. Alvarez A, Cerdá-Nicolás M, Naim Abu Nabah Y, et al. Direct evidence of leukocyte adhesion in arterioles by angiotensin Ⅱ. Blood, 2004, 104(2): 402-408.
5. 张加强, 魏长征, 吴祎, 等. 交联几丁糖治疗兔膝骨关节炎的实验研究. 中国修复重建外科杂志, 2019, 33(2): 185-189.
6. Han C, Liu J, Liu X, et al. Angiotensin Ⅱ induces C-reactive protein expression through ERK1/2 and JNK signaling in human aortic endothelial cells. Atherosclerosis, 2010, 212(1): 206-212.
7. Brzozowski T. Role of renin-angiotensin system and metabolites of angiotensin in the mechanism of gastric mucosal protection. Curr Opin Pharmacol, 2014, 19: 90-98.
8. Das UN. Angiotensin-Ⅱbehaves as an endogenous pro-inflammatory molecule. J Assoc Physicians India, 2005, 53: 472-476.
9. Zhang FY, Yang FJ, Yang JL, et al. Renin inhibition improves ovariectomy-induced osteoporosis of lumbar vertebra in mice. Biol Pharm Bull, 2014, 37(12): 1994-1997.
10. Byon IS, Lee DH, Jun ES, et al. Effect of angiotensin Ⅱ type 1 receptor blocker and angiotensin converting enzyme inhibitor on the intraocular growth factors and their receptors in streptozotocin-induced diabetic rats. Int J Ophthalmol, 2017, 10(6): 896-901.
11. Wu Y, Lu X, Li M, et al. Renin-angiotensin system in osteoarthritis: A new potential therapy. Int Immunopharmacol, 2019, 75: 105796.
12. Caspritz G, Alpermann HG, Schleyerbach R. Influence of the new angiotensin converting enzyme inhibitor ramipril on several models of acute inflammation and the adjuvant arthritis in the rat. Arzneimittelforschung, 1986, 36(11): 1605-1608.
13. Wang Y, Kou J, Zhang H, et al. The renin-angiotensin system in the synovium promotes periarticular osteopenia in a rat model of collagen-induced arthritis. Int Immunopharmacol, 2018, 65: 550-558.
14. Kohn MD, Sassoon AA, Fernando ND. Classifications in brief: Kellgren-Lawrence classification of osteoarthritis. Clin Orthop Relat Res, 2016, 474(8): 1886-1893.
15. Goldring SR. Alterations in periarticular bone and cross talk between subchondral bone and articular cartilage in osteoarthritis. Ther Adv Musculoskelet Dis, 2012, 4(4): 249-255.
16. Kawakami Y, Matsuo K, Murata M, et al. Expression of angiotensin Ⅱ receptor-1 in human articular chondrocytes. Arthritis, 2012, 2012: 648537.
17. Tsukamoto I, Akagi M, Inoue S, et al. Expression of local renin-angiotensin system components in chondrocytes. Eur J Histochem, 2014, 58(2): 2387.
18. Kawahata H, Sotobayashi D, Aoki M, et al. Continuous infusion of angiotensin Ⅱ modulates hypertrophic differentiation and apoptosis of chondrocytes in cartilage formation in a fracture model mouse. Hypertens Res, 2015, 38(6): 382-393.
19. Martin MF, Surrall KE, McKenna F, et al. Captopril: a new treatment for rheumatoid arthritis? Lancet, 1984, 1(8390): 1325-1328.
20. Walsh DA, Suzuki T, Knock GA, et al. AT1 receptor characteristics of angiotensin analogue binding in human synovium. Br J Pharmacol, 1994, 112(2): 435-442.
21. Silveira KD, Coelho FM, Vieira AT, et al. Mechanisms of the anti-inflammatory actions of the angiotensin type 1 receptor antagonist losartan in experimental models of arthritis. Peptides, 2013, 46: 53-63.
22. Kaschina E, Unger T. Angiotensin AT1/AT2 receptors: regulation, signalling and function. Blood Press, 2003, 12(2): 70-88.
23. Scott BB, Zaratin PF, Gilmartin AG, et al. TNF-alpha modulates angiopoietin-1 expression in rheumatoid synovial fibroblasts via the NF-kappa B signalling pathway. Biochem Biophys Res Commun, 2005, 328(2): 409-414.
24. Tang Y, Hu X, Lu X. Captopril, an angiotensin-converting enzyme inhibitor, possesses chondroprotective efficacy in a rat model of osteoarthritis through suppression local renin-angiotensin system. Int J Clin Exp Med, 2015, 8(8): 12584-12592.
25. Sagawa K, Nagatani K, Komagata Y, et al. Angiotensin receptor blockers suppress antigen-specific T cell responses and ameliorate collagen-induced arthritis in mice. Arthritis Rheum, 2005, 52(6): 1920-1928.

Chinese Journal of Reparative and Reconstructive Surgery

Expressions of Renin, angiotensin converting enzyme, angiotensin receptor 1, and angiotensin receptor 2 in synovial tissue of osteoarthritis at different stages

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