Research progress on protease-activated receptor 2 in pathogenesis of osteoarthritis_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

Lü Qinglie ¹ , GOU Yu ² ,  TIAN Faming ³ ,  ZHANG Liu ¹

1. Department of Orthopedics, Affiliated Hospital of North China University of Science and Technology, Tangshan Hebei, 063000, P.R.China;
2. Graduate School of Hebei Medical University, Shijiazhuang Hebei, 050017, P.R.China;
3. Medical Research Center, North China University of Science and Technology, Tangshan Hebei, 063000, P.R.China;

Corresponding?author：

TIAN Faming, Email: tfm9911316@163.com; ZHANG Liu, Email: Zhliu130@sohu.com

Keywords：

Osteoarthritis; protease-activated receptor 2; cytokine; joint; pain

DOI：

10.7507/1002-1892.201705025

Video：

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Objective To review the research progress on protease-activated receptor 2 (PAR-2) in the pathogenesis of osteoarthritis (OA). Methods The relevant literature about the mechanism of PAR-2 in the occurrence and development of OA in recent years was extensively reviewed and comprehensively analyzed. Results Abnormal activation of PAR-2 plays an important role in responses to occurrence and development of OA. Through regulating production and releasing of a variety of cytokines (such as inflammatory factors, metabolic factors, pain factors, etc.), the PAR-2 can involve in pathophysiological progression of OA articular cartilage, subchondral bone, and synovial membrane, as well as occurrence and transmission of pain. Conclusion PAR-2 participation in the development of OA has been confirmed. However, since PAR-2 is complicated and widespread, it is necessary to study the specific role of PAR-2 and the interaction between various signal pathways in the progression of OA, and to elucidate the potential pathophysiological mechanisms of PAR-2 participating in the process of OA, in the hope of exploring the new targets for the effective control of OA.

Citation： Lü Qinglie, GOU Yu, TIAN Faming, ZHANG Liu. Research progress on protease-activated receptor 2 in pathogenesis of osteoarthritis. Chinese Journal of Reparative and Reconstructive Surgery, 2017, 31(12): 1517-1522. doi: 10.7507/1002-1892.201705025 Copy

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2. 婁思權. 骨關節炎的病理與發病因素. 中華骨科雜志, 1996, 16(1): 56-59.
3. Puenpatom RA, Victor TW. Increased prevalence of metabolic syndrome in individuals with osteoarthritis: an analysis of NHANES III data. Postgrad Med, 2009, 121(6): 9-20.
4. Martel-Pelletier J, Battista JD, Lajeunesse D. Biochemical Factors in Joint Articular Tissue Degradation in Osteoarthritis. Berlin Heidelberg: Springer, 1999: 156-187.
5. Lam FF. Role of protease-activated receptor 2 in joint inflam-mation. Arthritis Rheum, 2007, 56(11): 3514-3517.
6. Xiang Y, Masuko-Hongo K, Sekine T, et al. Expression of proteinase-activated receptors (PAR)-2 in articular chondrocytes is modulated by IL-1beta, TNF-alpha and TGF-beta. Osteoarthritis Cartilage, 2006, 14(11): 1163-1173.
7. Steinhoff M, Vergnolle N, Young SH, et al. Agonists of proteinase-activated receptor 2 induce inflammation by a neurogenic mechanism. Nat Med, 2000, 6(2): 151-158.
8. Boileau C, Amiable N, Martel-Pelletier J, et al. Activation of proteinase-activated receptor 2 in human osteoarthritic cartilage upregulates catabolic and proinflammatory pathways capable of inducing cartilage degradation: a basic science study. Arthritis Res Ther, 2007, 9(6): R121.
9. Macfarlane SR, Seatter MJ, Kanke T, et al. Proteinase-activated receptors. Pharmacol Rev, 2001, 53(2): 245-282.
10. Coughlin SR. Thrombin signalling and protease-activated receptors. Nature, 2000, 407(6801): 258-264.
11. Coughlin SR, Camerer E. PARticipation in inflammation. J Clin Invest, 2003, 111(1): 25-27.
12. Nystedt S, Emilsson K, Wahlestedt C, et al. Molecular cloning of a potential proteinase activated receptor. Proc Natl Acad Sci U S A, 1994, 91(20): 9208-9212.
13. Trejo J. Protease-activated receptors: new concepts in regulation of G protein-coupled receptor signaling and trafficking. J Pharmacol Exp Ther, 2003, 307(2): 437-442.
14. 牛青霞, 何韶衡. 蛋白酶活化受體-2 的研究進展. 生理科學進展, 2003, 34(4): 373-375.
15. 馬怡茗, 趙新華, 包韓, 等. 蛋白酶活化受體 2 促進結腸癌細胞與基質粘附. 現代生物醫學進展, 2015, 15(5): 801-803.
16. 童曉紅, 丁家望. 蛋白酶活化受體-2 與心血管疾病的關系. 生命的化學, 2009, 29(3): 418-421.
17. 黃邵洪, 安軍, 李昀, 等. 激活蛋白酶活化受體 2 抑制肺癌細胞凋亡. 中國藥理學通報, 2014, 30 (5): 684-688.
18. Smith R, Ransj? M, Tatarczuch L, et al. Activation of protease-activated receptor-2 leads to inhibition of osteoclast differentiation. J Bone Miner Res, 2004, 19(3): 507-516.
19. Mackie EJ, Loh LH, Sivagurunathan S, et al. Protease-activated receptors in the musculoskeletal system. Int J Biochem Cell Biol, 2008, 40(6-7): 1169-1184.
20. Abraham LA, Chinni C, Jenkins AL, et al. Expression of protease-activated receptor-2 by osteoblasts. Bone, 2000, 26(1): 7-14.
21. Kelso EB, Ferrell WR, Lockhart JC, et al. Expression and proinflammatory role of proteinase-activated receptor 2 in rheumatoid synovium: ex vivo studies using a novel proteinase-activated receptor 2 antagonist. Arthritis Rheum, 2007, 56(3): 765-771.
22. Ferrell WR, Lockhart JC, Kelso EB, et al. Essential role for proteinase-activated receptor-2 in arthritis. J Clin Invest, 2003, 111(1): 35-41.
23. Busso N, Frasnelli M, Feifel R, et al. Evaluation of protease-activated receptor 2 in murine models of arthritis. Arthritis Rheum, 2007, 56(1): 101-107.
24. Belham CM, Tate RJ, Scott PH, et al. Trypsin stimulates proteinase-activated receptor-2-dependent and -independent activation of mitogen-activated protein kinases. Biochem J, 1996, 320 (Pt 3): 939-946.
25. Kanke T, Macfarlane SR, Seatter MJ, et al. Proteinase-activated receptor-2-mediated activation of stress-activated protein kinases and inhibitory kappa B kinases in NCTC 2544 keratinocytes. J Biol Chem, 2001, 276(34): 31657-31666.
26. Hirota Y, Osuga Y, Hirata T, et al. Activation of protease-activated receptor 2 stimulates proliferation and interleukin (IL)-6 and IL-8 secretion of endometriotic stromal cells. Hum Reprod, 2005, 20(12): 3547-3553.
27. Asokananthan N, Graham PT, Fink J, et al. Activation of protease-activated receptor (PAR)-1, PAR-2, and PAR-4 stimulates IL-6, IL-8, and prostaglandin E2 release from human respiratory epithelial cells. J Immunol, 2002, 168(7): 3577-3585.
28. Ramachandran R, Morice AH, Compton SJ. Proteinase-activated receptor2 agonists upregulate granulocyte colony-stimulating factor, IL-8, and VCAM-1 expression in human bronchial fibroblasts. Am J Respir Cell Mol Biol, 2006, 35(1): 133-141.
29. Huesa C, Ortiz AC, Dunning L, et al. Proteinase-activated receptor 2 modulates OA-related pain, cartilage and bone pathology. Ann Rheum Dis, 2016, 75(11): 1989-1997.
30. Milner JM, Patel A, Davidson RK, et al. Matriptase is a novel initiator of cartilage matrix degradation in osteoarthritis. Arthritis Rheum, 2010, 62(7): 1955-1966.
31. Osta B, Roux JP, Lavocat F, et al. Differential Effects of IL-17A and TNF-α on Osteoblastic Differentiation of Isolated Synoviocytes and on Bone Explants from Arthritis Patients. Front Immunol, 2015, 6: 151.
32. Shen S, Guo J, Luo Y, et al. Functional proteomics revealed IL-1β amplifies TNF downstream protein signals in human synoviocytes in a TNF-independent manner. Biochem Biophys Res Commun, 2014, 450(1): 538-544.
33. Ismail HM, Yamamoto K, Vincent TL, et al. Interleukin-1 Acts via the JNK-2 Signaling Pathway to Induce Aggrecan Degradation by Human Chondrocytes. Arthritis Rheumatol, 2015, 67(7): 1826-1836.
34. Attur MG, Patel IR, Patel RN, et al. Autocrine production of IL-1 beta by human osteoarthritis-affected cartilage and differential regulation of endogenous nitric oxide, IL-6, prostaglandin E2, and IL-8. Proc Assoc Am Physicians, 1998, 110(1): 65-72.
35. 高宗強, 郭雄, 陳君長, 等. 大骨節病、骨關節炎軟骨細胞分泌 IL-1β、TNF-α 及透明質酸對其影響實驗研究. 陜西醫學雜志, 2015, 44(7): 774-778.
36. Nystedt S, Ramakrishnan V, Sundelin J. The proteinase-activated receptor 2 is induced by inflammatory mediators in human endothelial cells. Comparison with the thrombin receptor. J Biol Chem, 1996, 271(25): 14910-14915.
37. 張延輝, 高春陽, 李少華. 骨性關節炎患者退變軟骨及滑膜組織中細胞因子的表達. 中國組織工程研究, 2013, 17(37): 6671-6675.
38. Arokoski JP, Lammi MJ, Hyttinen MM, et al. Etiopathogenesis of osteoarthritis. Duodecim, 2001, 117(16): 1617-1626.
39. Ju JH, Kang KY, Kim IJ, et al. Three-dimensional ultrasonographic application for analyzing synovial hypertrophy of the knee in patients with osteoarthritis. J Ultrasound Med, 2008, 27(5): 729-736.
40. Sasaki K, Takagi M, Konttinen YT, et al. Upregulation of matrix metalloproteinase (MMP)-1 and its activator MMP-3 of human osteoblast by uniaxial cyclic stimulation. J Biomed Mater Res B Appl Biomater, 2007, 80(2): 491-498.
41. Shiomi T, Lema?tre V, D’Armiento J, et al. Matrix metallo-proteinases, a disintegrin and metalloproteinases, and a disintegrin and metalloproteinases with thrombospondin motifs in non-neoplastic diseases. Pathol Int, 2010, 60(7): 477-496.
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