EFFECTS OF EXOGENOUS PROSTAGLANDIN E2 ON COLLAGEN CONTENT OF Achilles TENDON OF RABBITS IN VIVO_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

LI Hui , TANG Kanglai , DENG Yinshuan , XIE Meiming , CHANG Dehai , TAO Xu , XU Jianzhong

Department of Orthopedics, the Orthopedic Surgery Center of Chinese PLA, Southwest Hospital, the Third Military Medical University, Chongqing, 400038, P.R.China;

Corresponding author：

Keywords：

Prostaglandin E2; Tendinopathy; Collagen; Rabbit

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【Abstract】 Objective Prostaglandin E2 (PGE2) production increases in human tendon fibroblasts after the tendon injuries and repetitive mechanical loading in vitro. To analyze the relations between PGE2 and tendinopathy by observing the changes of collagen content and proportion after the Achilles tendon of rabbits is repeatedly exposed to PGE2. Methods Twenty-four Japanese rabbits (aged 3-4 months, weighing 2.0-2.5 kg, and male or female) were equally randomized into 2 groups according to injection dose of PGE2: low dose group (50 ng) and high dose group (500 ng). Corresponding PGE2 (0.2 mL) was injected into the middle segment of the Achilles tendon of hindlimb, the same dose saline into the same site of the other side as controls once a week for 4 weeks or 8 weeks. The Achilles tendons were harvested at 4 and 8 weeks after injection. HE staining was used to observe the cell structure and matrix, and picric acid-sirius red staining to observe the distribution and types of collagen fibers, and transmission electron microscopy was used to measure the density of the unit area and diameter of collagen fibers. Results HE staining showed that collagen structural damage was observed in low dose and high dose groups. Picric acid-sirius red staining showed that the content of type I collagen significantly decreased while the content of type III collagen significantly increased in experimental side of 2 groups at 4 and 8 weeks after injection when compared with control sides (P lt; 0.05). The content of type I collagen was significantly lower and the content of type III collagen and ratio of type III to type I were significantly higher in high dose group than in low dose group (P lt; 0.05). Transmission electron microscopy showed that the collagen fibers density of unit area was significantly lower and the diameter was significantly smaller in high dose and low dose groups than in the controls (P lt; 0.05), and in high dose group than in low dose group (P lt; 0.05). Conclusion Repeat exposure of the Achilles tendon of rabbit to PGE2 can cause the decrease of type I collagen, the increase of type III collagen, the reverse ratio of type I to type III, reduced unit density of collagen fibers, and thinner collagen fibers diameter, which is related with tendinopathy.

Citation： LI Hui,TANG Kanglai,DENG Yinshuan,XIE Meiming,CHANG Dehai,TAO Xu,XU Jianzhong. EFFECTS OF EXOGENOUS PROSTAGLANDIN E2 ON COLLAGEN CONTENT OF Achilles TENDON OF RABBITS IN VIVO. Chinese Journal of Reparative and Reconstructive Surgery, 2012, 26(3): 352-358. doi: Copy

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6.	Park JY, Pillinger MH, Abramson SB. Prostaglandin E2 synthesis and secretion: the role of PGE2 synthases. Clin Immunol, 2006, 119(3): 229-240.
7.	Yucel-Lindberg T, Olsson T, Kawakami T. Signal pathways involved in the regulation of prostaglandin E synthase-1 in human gingival fibroblasts. Cell Signal, 2006, 18(12): 2131-2142.
8.	Langberg H, Skovgaard D, Karamouzis M, et al. Metabolism and inflammatory mediators in the peritendinous space measured by microdialysis during intermittent isometric exercise in humans. J Physiol, 1999, 515(Pt3): 919-927.
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11.	Khan MH, Li Z, Wang JH. Repeated Exposure of tendon to prostaglandin-E2 leads to localized tendon degeneration. Clin J Sport Med, 2005, 15(1): 27-33.
12.	Wang JH. Mechanobiology of tendon. J Biomech, 2006, 39(9): 1563-1582.
13.	Oliva F, Via AG, Maffulli N. Calcific tendinopathy of the rotator cuff tendones. Sports Med Arthrosc, 2011, 19(3): 237-243.
14.	Arnoczky SP, Lavagnino M, Egerbacher M, et al. Matrix metalloproteinase inhibitors prevent a decrease in the mechanical properties of stress-deprived tendons: an in vitro experimental study. Am J Sports Med, 2007, 35(5): 763-769.
15.	曹洪辉, 唐康来, 陈磊, 等. 新型肌腱细胞循环牵伸载荷系统的研制及运行效果观察. 第三军医大学学报, 2010, 32(6): 507-510.
16.	邓银栓, 唐康来, 谢美明, 等. 不同牵伸载荷对体外培养人肌腱细胞纤维型肌动蛋白的影响. 中华医学杂志, 2011, 91(25): 1780-1785.
17.	谢美明, 唐康来, 邓银栓, 等. 不同牵伸强度对体外人肌腱细胞磷脂酶A2/环氧合酶表达的影响. 中华创伤杂志, 2011, 27(9): 822-826.
18.	Lui PP, Chan LS, Lee YW, et al. Sustained expression of proteoglycans and collagen type III/type I ratio in a calcified tendinopathy model. Rheumatology (Oxford), 2010, 49(2): 231-239.
19.	Riley G. Tendinopathy—from basic science to treatment. Nat Clin Pract Rheumatol, 2008, 4(2): 82-89.
20.	O’Keeffe SA, Hogan BA, Eustace SJ, et al. Overuse injuries of the knee. Magn Reson Imaging Clin N Am, 2009, 17(4): 725-739.
21.	Pearce CJ, Ismail M, Calder JD. Is apoptosis the cause of noninsertional achilles tendinopathy? Am J Sports Med, 2009, 37(12): 2440-2444.

1. Walz DM, Newman JS, Konin GP, et al. Epicondylitis: pathogenesis, imaging, and treatment. Radiographics, 2010, 30(1): 167-184.
2. Fredberg U, Stengaard-Pedersen K. Chronic tendinopathy tissue pathology, pain mechanisms, and etiology with a special focus on inflammation. Scand J Med Sci Sports, 2008, 18(1): 3-15.
3. Fu SC, Rolf C, Cheuk YC, et al. Deciphering the pathogenesis of tendinopathy: a three-stages process. Sports Med Arthrosc Rehabil Ther Technol, 2010, 2: 30.
4. Li Z, Yang G, Khan M, et al. Inflammatory response of human tendon fibroblasts to cyclic mechanical stretching. Am J Sports Med, 2004, 32(2): 435-440.
5. Bosetti F, Langenbach R, Weerasinghe GR. Prostaglandin E2 and microsomal prostaglandin E synthase-2 expression are decreased in the cyclooxygenase-2-deficient mouse brain despite compensatory induction of cyclooxygenase-1 and Ca2+-dependent phospholipase A2. J Neurochem, 2004, 91(6): 1389-1397.
6. Park JY, Pillinger MH, Abramson SB. Prostaglandin E2 synthesis and secretion: the role of PGE2 synthases. Clin Immunol, 2006, 119(3): 229-240.
7. Yucel-Lindberg T, Olsson T, Kawakami T. Signal pathways involved in the regulation of prostaglandin E synthase-1 in human gingival fibroblasts. Cell Signal, 2006, 18(12): 2131-2142.
8. Langberg H, Skovgaard D, Karamouzis M, et al. Metabolism and inflammatory mediators in the peritendinous space measured by microdialysis during intermittent isometric exercise in humans. J Physiol, 1999, 515(Pt3): 919-927.
9. Kjaer M, Langberg H, Heinemeier K, et al. From mechanical loading to collagen synthesis, structural changes and function in human tendon. Scand J Med Sci Sports, 2009, 19(4): 500-510.
10. Yao L, Bestwick CS, Bestwick LA, et al. Phenotypic drift in human tenocyte culture. Tissue Eng, 2006, 12(7): 1843-1849.
11. Khan MH, Li Z, Wang JH. Repeated Exposure of tendon to prostaglandin-E2 leads to localized tendon degeneration. Clin J Sport Med, 2005, 15(1): 27-33.
12. Wang JH. Mechanobiology of tendon. J Biomech, 2006, 39(9): 1563-1582.
13. Oliva F, Via AG, Maffulli N. Calcific tendinopathy of the rotator cuff tendones. Sports Med Arthrosc, 2011, 19(3): 237-243.
14. Arnoczky SP, Lavagnino M, Egerbacher M, et al. Matrix metalloproteinase inhibitors prevent a decrease in the mechanical properties of stress-deprived tendons: an in vitro experimental study. Am J Sports Med, 2007, 35(5): 763-769.
15. 曹洪辉, 唐康来, 陈磊, 等. 新型肌腱细胞循环牵伸载荷系统的研制及运行效果观察. 第三军医大学学报, 2010, 32(6): 507-510.
16. 邓银栓, 唐康来, 谢美明, 等. 不同牵伸载荷对体外培养人肌腱细胞纤维型肌动蛋白的影响. 中华医学杂志, 2011, 91(25): 1780-1785.
17. 谢美明, 唐康来, 邓银栓, 等. 不同牵伸强度对体外人肌腱细胞磷脂酶A2/环氧合酶表达的影响. 中华创伤杂志, 2011, 27(9): 822-826.
18. Lui PP, Chan LS, Lee YW, et al. Sustained expression of proteoglycans and collagen type III/type I ratio in a calcified tendinopathy model. Rheumatology (Oxford), 2010, 49(2): 231-239.
19. Riley G. Tendinopathy—from basic science to treatment. Nat Clin Pract Rheumatol, 2008, 4(2): 82-89.
20. O’Keeffe SA, Hogan BA, Eustace SJ, et al. Overuse injuries of the knee. Magn Reson Imaging Clin N Am, 2009, 17(4): 725-739.
21. Pearce CJ, Ismail M, Calder JD. Is apoptosis the cause of noninsertional achilles tendinopathy? Am J Sports Med, 2009, 37(12): 2440-2444.

Chinese Journal of Reparative and Reconstructive Surgery

EFFECTS OF EXOGENOUS PROSTAGLANDIN E2 ON COLLAGEN CONTENT OF Achilles TENDON OF RABBITS IN VIVO

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