DYNAMIC CHANGES OF MATRIX METALLOPROTEINASE 9 IN HETEROTOPIC OSSIFICATION OF RAT MODEL_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

SHIWeizhe ,  XIAOHaijun , XUEFeng , WUJiang

SHI Weizhe, XIAO Haijun, XUE Feng, WU Jiang;

Corresponding author：

XIAOHaijun, Email: xiaohaijun89@126.com

Keywords：

Matrix metalloproteinase 9; Heterotopic ossification; Extracellular matrix; Rat

DOI：

10.7507/1002-1892.20140246

Video：

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Objective To explore the value of matrix metalloproteinase 9 (MMP-9) in predicting the occurrence of heterotopic ossification by observing the expression of MMP-9 in heterotopic ossification of the early trauma rat model. Methods A total of 132 male Sprague Dawley rats, aged 4-5 weeks, weighing (135.0±6.5) g, were randomly divided into experimental group and control group (n=66). In experimental group, the Achilles tendon was cut off and clamped to prepare heterotopic ossification model; in control group, only Achilles tendon was exposed by making a incision. The general condition of the rats was observed after operation; at 2, 3, 4, 5, 6, 7, and 8 days after operation, the Achilles tendon tissue was harvested for gross observation, histological observation, and immunohistochemical staining observation; the serum and Achilles tendon tissue were harvested to detect the expressions of MMP-9 protein and mRNA by ELISA and RT-PCR. The X-ray films at 5 and 10 weeks and histological examination at 10 weeks after operation were used to observe heterotopic ossification. Results All rats survived to the end of the experiment. The Achilles tendon had no significant change in control group at each time point, showing normal tendon structure. In experimental group, the hardness of Achilles tendon tissue gradually increased with the time; there were a large number of irregular connective tissue and cartilage cells; and immunohistochemical staining for MMP-9 was positive results. The MMP-9 protein and mRNA expression levels of experimental group were significantly higher than those of the control group at each time point (P < 0.05). MMP-9 protein and mRNA expression levels of experimental group showed an increasing tendency (P < 0.05). According to the results of X-ray films and histological observation, heterotopic ossification occurred at 10 weeks after operation in experimental group, but no heterotopic ossification was observed in control group. Conclusion In early heterotopic ossification of rat Achilles tendon, the expression of MMP-9 increases significantly, indicating that it has reference significance in predicting heterotopic ossification.

Citation： SHIWeizhe, XIAOHaijun, XUEFeng, WUJiang. DYNAMIC CHANGES OF MATRIX METALLOPROTEINASE 9 IN HETEROTOPIC OSSIFICATION OF RAT MODEL. Chinese Journal of Reparative and Reconstructive Surgery, 2014, 28(9): 1133-1138. doi: 10.7507/1002-1892.20140246 Copy

1.	Peterson JR, Okagbare PI, De La Rosa S, et al.Early detection of burn induced heterotopic ossification using transcutaneous Raman spectroscopy.Bone, 2013, 54(1):28-34.
2.	Maldonado I, Reginato AM, Reginato AJ.Familial calcium crystal diseases:what have we learned?Curr Opin Rheumatol, 2001, 13(3):225-233.
3.	Rodenberg E, Azhdarinia A, Lazard ZW, et al.Matrixmetalloproteinase-9 is a diagnostic marker of heterotopic ossification in a murinemodel.Tissue Eng Part A, 2011, 17(19-20):2487-2496.
4.	Michelsson JE, Granroth G, Andersson LC.Myositis ossificans following forcible manipulation of the leg.A rabbit model for the study of heterotopic bone formation.J Bone Joint Surg (Br), 1980, 62(5):811-815.
5.	Lin L, Shen Q, Xue T, et al.Heterotopic ossification induced by Achilles tenotomy via endochondral bone formation:expression of bone and cartilage related genes.Bone, 2010, 46(2):425-431.
6.	吴江, 肖海军, 薛锋, 等.选择性与非选择性环氧化酶2抑制剂预防大鼠跟腱异位骨化的实验研究.中国修复重建外科杂志, 2014, 28(3):371-376.
7.	徐俊昌, 吴涛, 吴桂华, 等.跟腱切断法诱导大鼠异位骨化动物模型的建立.中国矫形外科杂志, 2009, 17(8):625-627.
8.	Sethi CS, Bailey TA, Luthert PJ, et al.Matrix metalloproteinase biology applied to vitreoretinal disorders.Br J Ophthalmol, 2000, 84(6):654-666.
9.	Visse R, Nagase H.Matrix metalloproteinases and tissue inhibitors of metalloproteinases:structure, function, and biochemistry.Circ Res, 2003, 92(8):827-839.
10.	Carla Oliveira de Oliveira, Nilo Ikuta, Andrea Regner.Outcome biomarkers following severe traumatic brain injury.Rev Bras Intensiva, 2008, 20(4):411-421.
11.	Yager DR, Nwomeh BC.The proteolytic environment of chronic wounds.Wound Repair Regen, 1999, 7(6):433-441.
12.	Parks WC.Matrix metalloproteinases in repair.Wound Repair Regen, 1999, 7(6):423-432.
13.	Parsons SL, Watson SA, Brown PD, et al.Matrix metalloproteinases.Br J Surg, 1997, 84(2):160-166.
14.	Gupta K, Shukla M, Cowland JB, et al.Neutrophil gelatinase-associated lipocalin is expressed in osteoarthritis and forms a complex with matrix metalloproteinase 9.Arthritis Rheum, 2007, 56(10):3326-3335.
15.	Kuehl P, Zhang J, Lin Y, et al.Sequence diversity in CYP3A promoters and characterization of the genetic basis of polymorphic CYP3A5 expression.Nat Genet, 2001, 27(4):383-391.
16.	王福科, 李彦林, 朱晓松, 等.中枢神经损伤与异位骨化.中国修复重建外科杂志, 2006, 20(8):854-857.
17.	Chakraborti S, Mandal M, Das S, et al.Regulation of matrix metalloproteinases:an overview.Mol Cell Biochem, 2003, 253(1-2):269-285.
18.	Li DQ, Lokeshwar BL, Solomon A, et al.Regulation of MMP-9 production by human corneal epithelial cells.Exp Eye Res, 2001, 73(4):449-459.
19.	Urist MR, Nakagawa M, Nakata N, et al.Experimental myositis ossificans:cartilage and bone formation in muscle in response to a diffusible bone matrix-derived morphogen.Arch Pathol Lab Med, 1978, 102(6):312-316.
20.	Midy V, Plouët J.Vasculotropin/vascular endothelial growth factor induces differentiation in cultured osteoblasts.Biochem Biophys Res Commun, 1994, 199(1):380-386.
21.	Buschbacher R, McKinley W, Buschbacher L, et al.Warfarin in prevention of heterotopic ossification.Am J Phys Med Rehabil, 1992, 71(2):86-91.

1. Peterson JR, Okagbare PI, De La Rosa S, et al.Early detection of burn induced heterotopic ossification using transcutaneous Raman spectroscopy.Bone, 2013, 54(1):28-34.
2. Maldonado I, Reginato AM, Reginato AJ.Familial calcium crystal diseases:what have we learned?Curr Opin Rheumatol, 2001, 13(3):225-233.
3. Rodenberg E, Azhdarinia A, Lazard ZW, et al.Matrixmetalloproteinase-9 is a diagnostic marker of heterotopic ossification in a murinemodel.Tissue Eng Part A, 2011, 17(19-20):2487-2496.
4. Michelsson JE, Granroth G, Andersson LC.Myositis ossificans following forcible manipulation of the leg.A rabbit model for the study of heterotopic bone formation.J Bone Joint Surg (Br), 1980, 62(5):811-815.
5. Lin L, Shen Q, Xue T, et al.Heterotopic ossification induced by Achilles tenotomy via endochondral bone formation:expression of bone and cartilage related genes.Bone, 2010, 46(2):425-431.
6. 吴江, 肖海军, 薛锋, 等.选择性与非选择性环氧化酶2抑制剂预防大鼠跟腱异位骨化的实验研究.中国修复重建外科杂志, 2014, 28(3):371-376.
7. 徐俊昌, 吴涛, 吴桂华, 等.跟腱切断法诱导大鼠异位骨化动物模型的建立.中国矫形外科杂志, 2009, 17(8):625-627.
8. Sethi CS, Bailey TA, Luthert PJ, et al.Matrix metalloproteinase biology applied to vitreoretinal disorders.Br J Ophthalmol, 2000, 84(6):654-666.
9. Visse R, Nagase H.Matrix metalloproteinases and tissue inhibitors of metalloproteinases:structure, function, and biochemistry.Circ Res, 2003, 92(8):827-839.
10. Carla Oliveira de Oliveira, Nilo Ikuta, Andrea Regner.Outcome biomarkers following severe traumatic brain injury.Rev Bras Intensiva, 2008, 20(4):411-421.
11. Yager DR, Nwomeh BC.The proteolytic environment of chronic wounds.Wound Repair Regen, 1999, 7(6):433-441.
12. Parks WC.Matrix metalloproteinases in repair.Wound Repair Regen, 1999, 7(6):423-432.
13. Parsons SL, Watson SA, Brown PD, et al.Matrix metalloproteinases.Br J Surg, 1997, 84(2):160-166.
14. Gupta K, Shukla M, Cowland JB, et al.Neutrophil gelatinase-associated lipocalin is expressed in osteoarthritis and forms a complex with matrix metalloproteinase 9.Arthritis Rheum, 2007, 56(10):3326-3335.
15. Kuehl P, Zhang J, Lin Y, et al.Sequence diversity in CYP3A promoters and characterization of the genetic basis of polymorphic CYP3A5 expression.Nat Genet, 2001, 27(4):383-391.
16. 王福科, 李彦林, 朱晓松, 等.中枢神经损伤与异位骨化.中国修复重建外科杂志, 2006, 20(8):854-857.
17. Chakraborti S, Mandal M, Das S, et al.Regulation of matrix metalloproteinases:an overview.Mol Cell Biochem, 2003, 253(1-2):269-285.
18. Li DQ, Lokeshwar BL, Solomon A, et al.Regulation of MMP-9 production by human corneal epithelial cells.Exp Eye Res, 2001, 73(4):449-459.
19. Urist MR, Nakagawa M, Nakata N, et al.Experimental myositis ossificans:cartilage and bone formation in muscle in response to a diffusible bone matrix-derived morphogen.Arch Pathol Lab Med, 1978, 102(6):312-316.
20. Midy V, Plouët J.Vasculotropin/vascular endothelial growth factor induces differentiation in cultured osteoblasts.Biochem Biophys Res Commun, 1994, 199(1):380-386.
21. Buschbacher R, McKinley W, Buschbacher L, et al.Warfarin in prevention of heterotopic ossification.Am J Phys Med Rehabil, 1992, 71(2):86-91.

Chinese Journal of Reparative and Reconstructive Surgery

DYNAMIC CHANGES OF MATRIX METALLOPROTEINASE 9 IN HETEROTOPIC OSSIFICATION OF RAT MODEL

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