EXPRESSIONS OF LIGAMENT REMODELING RELATED GENES IN RABBIT MODEL OF ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION WITH PRESERVING TIBIAL RESIDUAL FIBERS_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

XIEGuoming , DONGShikui , HUANGFUXiaoqiao ,  ZHAOJinzhong

Department of Sports Medicine, Affiliated Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, 200233, P. R. China;

Corresponding author：

ZHAOJinzhong, Email: zhaojinzhong@vip.163.com

Keywords：

Preservation remnant; Anterior cruciate ligament reconstruction; Ligamentization; Gene expression; Rabbit

DOI：

10.7507/1002-1892.20160004

Video：

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Objective To observe the effect of preserving tibial residual fibers on the expressions of ligament remodeling related genes in rabbit anterior cruciate ligament (ACL) reconstruction model. Methods Sixty healthy adult New Zealand white rabbits were randomly divided into 4 groups:normal control group (group A, n=6) , sham-operation group (group B, n=18) , non tibial remnant preserved group (group C, n=18) , and tibial remnant preserved group (group D, n=18) . At 2, 6, and 12 weeks after operation, the ligament tissue was harvested to detect the mRNA expressions of collagen type 1A1(COL1A1) , collagen type 3A1(COL3A1) , transforming growth factor β₁(TGF-β₁), vascular endothelial growth factor (VEGF), growth-associated protein 43(GAP-43) , and neurotrophin 3(NT-3) by real-time fluorescent quantitative PCR. Results At each time point, there was no significant difference in the mRNA expressions of COL1A1, COL3A1, VEGF, and NT-3 between group A and group B (P>0.05) . In group D, the mRNA expressions of COL1A1, COL3A1, TGF-β₁, and GAP-43 significantly increased when compared with those of group C at 6 weeks after operation (P＜0.05) ; an increased level of VEGF mRNA was also detected in the group D at 12 weeks after operation (P＜0.05) ; and an increased level of NT-3 mRNA was also observed in group D at 2 and 12 weeks after operation (P＜0.05) . Conclusion There is a time-dependent manner of angiogenesis-promoting, repair-related, and nerve-related gene expressions after ACL reconstruction with preserving tibial residual fibers during the process of ligamentization. Furthermore, the remnant preservation in ACL reconstruction can promote the expressions of related genes in some time points.

Citation： XIEGuoming, DONGShikui, HUANGFUXiaoqiao, ZHAOJinzhong. EXPRESSIONS OF LIGAMENT REMODELING RELATED GENES IN RABBIT MODEL OF ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION WITH PRESERVING TIBIAL RESIDUAL FIBERS. Chinese Journal of Reparative and Reconstructive Surgery, 2016, 30(1): 15-20. doi: 10.7507/1002-1892.20160004 Copy

1.	Lee BI, Kwon SW, Kim JB, et al. Comparison of clinical results according to amount of preserved remnant in arthroscopic anterior cruciate ligament reconstruction using quadrupled hamstring graft. Arthroscopy, 2008, 24(5):560-568.
2.	Lee BI, Min KD, Choi HS, et al. Immunohistochemical study of mechanoreceptors in the tibial remnant of the ruptured anterior cruciate ligament in human knees. Knee Surg Sports Traumatol Arthrosc, 2009, 17(9):1095-1101.
3.	Nguyen DT, Ramwadhdoebe TH, van der Hart CP, et al. Intrinsic healing response of the human anterior cruciate ligament:an histological study of reattached ACL remnants. J Orthop Res, 2014, 32(2):296-301.
4.	Junkin DM Jr, Johnson DL. ACL tibial remnant, to save or not? Orthopedics, 2008, 31(2):154-159.
5.	Grana WA, Egle DM, Mahnken R, et al. An analysis of autograft fixation after anterior cruciate ligament reconstruction in a rabbit model. Am J Sports Med, 1994, 22(3):344-351.
6.	Wiig M, Amiel D, Ivarsson M, et al. Type I procollagen gene expression in normal and early healing of the medial collateral and anterior cruciate ligaments in rabbits:an in situ hybridization study. J Orthop Res, 1991, 9(3):374-382.
7.	Spindler K, Clark S, Nanney L, et al. Expression of collagen and matrix metalloproteinases in ruptured human anterior cruciate ligament:an in situ hybridization study. J Orthop Res, 1996, 14(6):857-861.
8.	Tohyama H, Yasuda K, Uchida H. Is the increase in type III collagen of the patellar tendon graft after ligament reconstruction really caused by ligamentization of the graft? Knee Surg Sports Traumatol Arthrosc, 2006, 14(12):1270-1277.
9.	Petersen W, Unterhauser F, Pufe T, et al. A The angiogenic peptide vascular endothelial growth factor (VEGF) is expressed during the remodeling of free tendon grafts in sheep. Arch Orthop Trauma Surg, 2003, 123(4):168-174.
10.	Yoshikawa T, Tohyama H, Enomoto H, et al. Expression of vascular endothelial growth factor and angiogenesis in patellar tendon grafts in the early phase after anterior cruciate ligament reconstruction. Knee Surg Sports Traumatol Arthrosc, 2006, 14(9):804-810.
11.	Ferrara N, Davis-Smyth T. The biology of vascular endothelial growth factor. Endocr Rev, 1997, 18(1):4-25.
12.	Jośko J, Mazurek M. Transcription factors having impact on vascular endothelial growth factor (VEGF) gene expression in angiogenesis. Med Sci Monit, 2004, 10(4):RA89-RA98.
13.	Gohil S, Annear P, Breidahl W. Anterior cruciate ligament reconstruction using autologous double hamstrings:a comparison of standard versus minimal debridement techniques using MRI to assess revascularization. A randomized prospective study with a one-year follow-up. J Bone Joint Surg (Br), 2007, 89(9):1165-1171.
14.	Kim IY, Kim MM, Kim S. Transforming growth factor-beta:biology and clinical relevance. J Biochem Mol Biol, 2005, 38(1):1-8.
15.	Kuroda R, Kurosaka M, Yoshiya S, et al. Localization of growth factors in the reconstructed anterior cruciate ligament:immunohistological study in dogs. Knee Surg Sports Traumatol Arthrosc, 2000, 8(2):120-126.
16.	Beye JA, Hart DA, Bray RC, et al. Injury-induced changes in mRNA levels differ widely between anterior cruciate ligament and medial collateral ligament. Am J Sports Med, 2008, 36(7):1337-1346.
17.	Aune AK, Hukkanen M, Madsen JE, et al. Nerve regeneration during patellar tendon autograft emodeling after anterior cruciate ligament reconstruction:an experimental and clinical study. J Orthop Res, 1996, 14(2):193-199.
18.	Chen LJ, Ren YH, Liu L, et al. Upregulated expression of GAP-43 mRNA and protein in anterior horn motoneurons of the spinal cord after brachial plexus injury. Arch Med Res, 2010, 41(7):513-518.
19.	Perez-Pinera P, García-Suarez O, Germanà A, et al. Characterization of sensory deficits in TrkB knockout mice. Neurosc Lett, 2008, 433(1):43-47.
20.	Sterne GD, Brown RA, Green CJ, et al. Neurotrophin-3 delivered locally via fibronectin mats enhances peripheral nerve regeneration. Eur J Neurosci, 1997, 9(7):1388-1396.
21.	Copray J, Brouwer N. Neurotrophin-3 mRNA expression in rat intrafusal muscle fibres after denervation and reinnervation. Neurosci Lett, 1997, 236(1):41-44.

1. Lee BI, Kwon SW, Kim JB, et al. Comparison of clinical results according to amount of preserved remnant in arthroscopic anterior cruciate ligament reconstruction using quadrupled hamstring graft. Arthroscopy, 2008, 24(5):560-568.
2. Lee BI, Min KD, Choi HS, et al. Immunohistochemical study of mechanoreceptors in the tibial remnant of the ruptured anterior cruciate ligament in human knees. Knee Surg Sports Traumatol Arthrosc, 2009, 17(9):1095-1101.
3. Nguyen DT, Ramwadhdoebe TH, van der Hart CP, et al. Intrinsic healing response of the human anterior cruciate ligament:an histological study of reattached ACL remnants. J Orthop Res, 2014, 32(2):296-301.
4. Junkin DM Jr, Johnson DL. ACL tibial remnant, to save or not? Orthopedics, 2008, 31(2):154-159.
5. Grana WA, Egle DM, Mahnken R, et al. An analysis of autograft fixation after anterior cruciate ligament reconstruction in a rabbit model. Am J Sports Med, 1994, 22(3):344-351.
6. Wiig M, Amiel D, Ivarsson M, et al. Type I procollagen gene expression in normal and early healing of the medial collateral and anterior cruciate ligaments in rabbits:an in situ hybridization study. J Orthop Res, 1991, 9(3):374-382.
7. Spindler K, Clark S, Nanney L, et al. Expression of collagen and matrix metalloproteinases in ruptured human anterior cruciate ligament:an in situ hybridization study. J Orthop Res, 1996, 14(6):857-861.
8. Tohyama H, Yasuda K, Uchida H. Is the increase in type III collagen of the patellar tendon graft after ligament reconstruction really caused by ligamentization of the graft? Knee Surg Sports Traumatol Arthrosc, 2006, 14(12):1270-1277.
9. Petersen W, Unterhauser F, Pufe T, et al. A The angiogenic peptide vascular endothelial growth factor (VEGF) is expressed during the remodeling of free tendon grafts in sheep. Arch Orthop Trauma Surg, 2003, 123(4):168-174.
10. Yoshikawa T, Tohyama H, Enomoto H, et al. Expression of vascular endothelial growth factor and angiogenesis in patellar tendon grafts in the early phase after anterior cruciate ligament reconstruction. Knee Surg Sports Traumatol Arthrosc, 2006, 14(9):804-810.
11. Ferrara N, Davis-Smyth T. The biology of vascular endothelial growth factor. Endocr Rev, 1997, 18(1):4-25.
12. Jośko J, Mazurek M. Transcription factors having impact on vascular endothelial growth factor (VEGF) gene expression in angiogenesis. Med Sci Monit, 2004, 10(4):RA89-RA98.
13. Gohil S, Annear P, Breidahl W. Anterior cruciate ligament reconstruction using autologous double hamstrings:a comparison of standard versus minimal debridement techniques using MRI to assess revascularization. A randomized prospective study with a one-year follow-up. J Bone Joint Surg (Br), 2007, 89(9):1165-1171.
14. Kim IY, Kim MM, Kim S. Transforming growth factor-beta:biology and clinical relevance. J Biochem Mol Biol, 2005, 38(1):1-8.
15. Kuroda R, Kurosaka M, Yoshiya S, et al. Localization of growth factors in the reconstructed anterior cruciate ligament:immunohistological study in dogs. Knee Surg Sports Traumatol Arthrosc, 2000, 8(2):120-126.
16. Beye JA, Hart DA, Bray RC, et al. Injury-induced changes in mRNA levels differ widely between anterior cruciate ligament and medial collateral ligament. Am J Sports Med, 2008, 36(7):1337-1346.
17. Aune AK, Hukkanen M, Madsen JE, et al. Nerve regeneration during patellar tendon autograft emodeling after anterior cruciate ligament reconstruction:an experimental and clinical study. J Orthop Res, 1996, 14(2):193-199.
18. Chen LJ, Ren YH, Liu L, et al. Upregulated expression of GAP-43 mRNA and protein in anterior horn motoneurons of the spinal cord after brachial plexus injury. Arch Med Res, 2010, 41(7):513-518.
19. Perez-Pinera P, García-Suarez O, Germanà A, et al. Characterization of sensory deficits in TrkB knockout mice. Neurosc Lett, 2008, 433(1):43-47.
20. Sterne GD, Brown RA, Green CJ, et al. Neurotrophin-3 delivered locally via fibronectin mats enhances peripheral nerve regeneration. Eur J Neurosci, 1997, 9(7):1388-1396.
21. Copray J, Brouwer N. Neurotrophin-3 mRNA expression in rat intrafusal muscle fibres after denervation and reinnervation. Neurosci Lett, 1997, 236(1):41-44.

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Chinese Journal of Reparative and Reconstructive Surgery

EXPRESSIONS OF LIGAMENT REMODELING RELATED GENES IN RABBIT MODEL OF ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION WITH PRESERVING TIBIAL RESIDUAL FIBERS

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