A correlation study between the Mohawk expression level and the collagen fiber diameter of hamstring tendon graft after anterior cruciate ligament reconstruction_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

LI Ying ^1,2 , WU Bing ^1,2 , QIU Zhihe ¹ , LIANG Daqiang ^1,2 , LIU Haifeng ^1,2 , ZHONG Mingjin ^1,2 , XU Jian ^1,2 , CHEN Kang ^1,2 , FENG Wenzhe ^1,2 , LI Hao ^1,2 , PENG Liangquan ^1,2 , OUYANG Kan ^1,2 , ZHU Weimin ^1,2 ,  LU Wei ^1,2 ,  WANG Daping ^1,2

1. Department of Sports Medicine, the First Affiliated Hospital of Shenzhen University (Shenzhen Second People’s Hospital), Shenzhen Guangdong, 518000, P.R.China;
2. Sports Medicine Engineering Technology Research Center of Guangdong Province, Shenzhen Guangdong, 518000, P.R.China;

Corresponding author：

LU Wei, Email: winerl@sina.com; WANG Daping, Email: dapingwang@medmail.com.cn

Keywords：

Anterior cruciate ligament reconstruction; graft remodeling; Mohawk; collagen fiber; ultrastructure

DOI：

10.7507/1002-1892.201902040

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Objective To evaluate the correlation between the Mohawk (MKX) expression level and the collagen fiber diameter of autologous hamstring tendon graft during the stable graft remodeling phase after anterior cruciate ligament (ACL) reconstruction.Methods Between January 2018 and August 2018, patients who underwent arth-roscopic single-bundle anatomical ACL reconstruction with autologous hamstring tendons for at least 48 months and also underwent second-look arthroscopy were enrolled in study. During the second-look arthroscopic procedures, ACL graft biopsies were performed from the surface of central part of the ligament. MKX expressions of ACL grafts were analysed by real-time fluorescent quantitative PCR (qRT-PCR). The ultrastructure of collagen fibers of grafts were evaluated by transmission electron microscopy, which included average diameter of collagen fibers (D_c), average diameter of large-diameter collagen fibers (D_L), average diameter of small-diameter collagen fibers (D_S), and large-small collagen fibers ratio (R_L/S). The correlation between MKX expression level and graft collagen fiber diameter was calculated.Results Twenty-six patients met the selection criteria and their ACL graft specimens were enrolled in the study. The interval between ACL reconstruction and second-look arthroscopy was 52-128 months, with an average of 78.6 months. Arthroscopic graft remodeling score was 3-6 (mean, 4.8). There were 17 cases of excellent remodeling and 9 cases of fair remodeling. All ACL grafts showed typical bimodal distributions of both large-diameter collagen fibers and small-diameter collagen fibers, but the ultrastructural characteristics of the graft collagen fibers were different according to different remodeling status under arthroscopy. The D_C, D_L, D_S, and R_L/S of the graft specimens were (65.2±9.3) nm, (91.6±10.5) nm, (45.7±8.6) nm, and 0.73±0.12, respectively. The relative expression level of MKX was 1.42±0.11, which was positively linearly correlated with D_C, D_L, and R_L/S, and the correlation coefficient was statistically significant (r=0.809, P=0.000; r=0.861, P=0.000; r=0.942, P=0.000), while there was no significant correlation between D_S and relative expression level of MKX (r=0.147, P=0.238). Regression analysis showed that the relative expression level of MKX could predict the D_C, D_L, and R_L/S results of the ACL graft specimens (P<0.05).Conclusion After autologous hamstring tendon grafts stepped into stabilized remodeling phase, MKX expression level could predict the diameter measurement results of collagen fibers and be used as an important evaluation basis for graft collagen anabolic metabolism.

Citation： LI Ying, WU Bing, QIU Zhihe, LIANG Daqiang, LIU Haifeng, ZHONG Mingjin, XU Jian, CHEN Kang, FENG Wenzhe, LI Hao, PENG Liangquan, OUYANG Kan, ZHU Weimin, LU Wei, WANG Daping. A correlation study between the Mohawk expression level and the collagen fiber diameter of hamstring tendon graft after anterior cruciate ligament reconstruction. Chinese Journal of Reparative and Reconstructive Surgery, 2019, 33(9): 1095-1101. doi: 10.7507/1002-1892.201902040 Copy

1.	Pinczewski L, Roe J, Salmon L. Why autologous hamstring tendon reconstruction should now be considered the gold standard for anterior cruciate ligament reconstruction in athletes. Br J Sports Med, 2009, 43(5): 325-327.
2.	Tian S, Wang Y, Wang B, et al. Anatomic double-bundle anterior cruciate ligament reconstruction with a hamstring tendon autograft and fresh-frozen allograft: a prospective, randomized, and controlled study. Arthroscopy, 2016, 32(12): 2521-2531.
3.	Lee JK, Lee S, Lee MC. Outcomes of anatomic anterior cruciate ligament reconstruction: bone-quadriceps tendon graft versus double-bundle hamstring tendon graft. Am J Sports Med, 2016, 44(9): 2323-2329.
4.	Amiel D, Kleiner JB, Roux RD, et al. The phenomenon of " ligamentization”: anterior cruciate ligament reconstruction with autogenous patellar tendon. J Orthop Res, 1986, 4(2): 162-172.
5.	Claes S, Verdonk P, Forsyth R, et al. The " ligamentization” process in anterior cruciate ligament reconstruction: what happens to the human graft? A systematic review of the literature. Am J Sports Med, 2011, 39(11): 2476-2483.
6.	Scheffler SU, Unterhauser FN, Weiler A. Graft remodeling and ligamentization after cruciate ligament reconstruction. Knee Surg Sports Traumatol Arthrosc, 2008, 16(9): 834-842.
7.	Papageorgiou CD, Ma CB, Abramowitch SD, et al. A multi disciplinary study of the healing of an intraarticular anterior cruciate ligament graft in a goat model. Am J Sports Med, 2001, 29(5): 620-626.
8.	Cho S, Muneta T, Ito S, Y, et al. Electron microscopic evaluation of two-bundle anatomically reconstructed anterior cruciate ligament graft. J Orthop Sci, 2004, 9(3): 296-301.
9.	Marumo K, Saito M, Yamagishi T, et al. The " Ligamentization” process in human anterior cruciate ligament reconstruction with autogenous patellar and hamstring tendons: a biochemical study. Am J Sports Med, 2005, 33(8): 1166-1173.
10.	Cribb AM, Scott JE. Tendon response to tensile stress: an ultrastructural investigation of collagen: proteoglycan interactions in stressed tendon. J Anat, 1995, 187(Pt 2): 423-428.
11.	Wells HC, Edmonds RL, Kirby N, et al. Collagen fibril diameter and leather strength. J Agric Food Chem, 2013, 61(47): 11524-11531.
12.	Parry DA, Barnes GR, Craig AS. A comparison of the size distribution of collagen fibrils in connective tissues as a function of age and a possible relation between fibril size distribution and mechanical properties. Proc R Soc Lond B Biol Sci, 1978, 203(1152): 305-321.
13.	Goodship AE, Birch HL, Wilson AM. The pathobiology and repair of tendon and ligament injury. Vet Clin North Am Equine Pract, 1994, 10(2): 323-349.
14.	Anderson DM, Arredondo J, Hahn K, et al. Mohawk is a novel homeobox gene expressed in the developing mouse embryo. Dev Dyn, 2006, 235(3): 792-801.
15.	Liu H, Liu W, Maltby KM, et al. Identification and developmental expression analysis of a novel homeobox gene closely linked to the mouse twirler mutation. Gene Expr Patterns, 2006, 6(6): 632-636.
16.	吴冰, 许美权, 李盛, 等. 关节镜下不同塑形状态前交叉韧带移植物 Mohawk 转录因子及胶原表达差异的研究. 中华创伤骨科杂志, 2018, 20(5): 529-536.
17.	吴冰, 陆伟, 王大平, 等. 前交叉韧带重建术后 MRI 评分与临床膝关节主、客观功能评分的对比研究. 中国临床解剖学杂志, 2016, 34(6): 677-684.
18.	Kondo E, Yasuda K. Second-look arthroscopic evaluations of anatomic double-bundle anterior cruciate ligament reconstruction: relation with postoperative knee stability. Arthroscopy, 2007, 23(11): 1198-1209.
19.	Lee JH, Bae DK, Song SJ, et al. Comparison of clinical results and second-look arthroscopy findings after arthroscopic anterior cruciate ligament reconstruction using 3 different types of grafts. Arthroscopy, 2010, 26(1): 41-49.
20.	Zaffagnini S, De Pasquale V, Marchesini Reggiani L, et al. Electron microscopy of the remodelling process in hamstring tendon used as ACL graft. Knee Surg Sports Traumatol Arthrosc, 2010, 18(8): 1052-1058.
21.	Abe S, Kurosaka M, Iguchi T, et al. Light and electron microscopic study of remodeling and maturation process in autogenous graft for anterior cruciate ligament reconstruction. Arthroscopy, 1993, 9(4): 394-405.
22.	Sánchez M, Anitua E, Azofra J, et al. Ligamentization of tendon grafts treated with an endogenous preparation rich in growth factors: gross morphology and histology. Arthroscopy, 2010, 26(4): 470-480.
23.	Rougraff B, Shelbourne KD, Gerth PK, et al. Arthroscopic and histologic analysis of human patellar tendon autografts used for anterior cruciate ligament reconstruction. Am J Sports Med, 1993, 21(2): 277-284.
24.	Strocchi R, de Pasquale V, Gubellini P, et al. The human anterior cruciate ligament: histological and ultrastructural observations. J Anat, 1992, 180(Pt 3): 515-519.
25.	Shino K, Oakes BW, Horibe S, et al. Collagen fibril populations in human anterior cruciate ligament allografts. Electron microscopic analysis. Am J Sports Med, 1995, 23(2): 203-209.
26.	Frogameni AD, Jack son DW. Collagen remodelling in ACL reconstruction//The anterior cruciate ligament: current and future concepts. New York: Raven Press, 1993: 219-220.
27.	Shino K, Oaes B, Inone M, et al. Human allografts collage fibril populations as a function of age of the graft. Trans Orthop Res Sco, 1990, 15(4): 520.
28.	Shadwick RE. Elastic energy storage in tendons: mechanical differences related to function and age. J Appl Physiol (1985), 1990, 68(3): 1033-1040.
29.	Jackson DW, Grood ES, Goldstein JD, et al. A comparison of patellar tendon autograft and allograft used for anterior cruciate ligament reconstruction in the goat model. Am J Sports Med, 1993, 21(2): 176-185.
30.	Butler DL, Grood ES, Noyes FR, et al. On the interpretation of our anterior cruciate ligament data. Clin Orthop Relat Res, 1985, (196): 26-34.
31.	Kennedy JC, Hawkins RJ, Willis RB, et al. Tension studies of human knee ligaments. Yield point, ultimate failure, and disruption of the cruciate and tibial collateral ligaments. J Bone Joint Surg (Am), 1976, 58(3): 350-355.
32.	Dong S, Xie G, Zhang Y, et al. Ligamentization of autogenous hamstring grafts after anterior cruciate ligament reconstruction: midterm versus long-term results. Am J Sports Med, 2015, 43(8): 1908-1917.
33.	夏春, 张兵, 王少杰, 等. 前十字韧带重建术后自体 Hamstring 腱的超微结构研究. 中华骨科杂志, 2009, 29(3): 248-251.
34.	Nakahara H, Hasegawa A, Otabe K, et al. Transcription factor Mohawk and the pathogenesis of human anterior cruciate ligament degradation. Arthritis Rheum, 2013, 65(8): 2081-2089.

1. Pinczewski L, Roe J, Salmon L. Why autologous hamstring tendon reconstruction should now be considered the gold standard for anterior cruciate ligament reconstruction in athletes. Br J Sports Med, 2009, 43(5): 325-327.
2. Tian S, Wang Y, Wang B, et al. Anatomic double-bundle anterior cruciate ligament reconstruction with a hamstring tendon autograft and fresh-frozen allograft: a prospective, randomized, and controlled study. Arthroscopy, 2016, 32(12): 2521-2531.
3. Lee JK, Lee S, Lee MC. Outcomes of anatomic anterior cruciate ligament reconstruction: bone-quadriceps tendon graft versus double-bundle hamstring tendon graft. Am J Sports Med, 2016, 44(9): 2323-2329.
4. Amiel D, Kleiner JB, Roux RD, et al. The phenomenon of " ligamentization”: anterior cruciate ligament reconstruction with autogenous patellar tendon. J Orthop Res, 1986, 4(2): 162-172.
5. Claes S, Verdonk P, Forsyth R, et al. The " ligamentization” process in anterior cruciate ligament reconstruction: what happens to the human graft? A systematic review of the literature. Am J Sports Med, 2011, 39(11): 2476-2483.
6. Scheffler SU, Unterhauser FN, Weiler A. Graft remodeling and ligamentization after cruciate ligament reconstruction. Knee Surg Sports Traumatol Arthrosc, 2008, 16(9): 834-842.
7. Papageorgiou CD, Ma CB, Abramowitch SD, et al. A multi disciplinary study of the healing of an intraarticular anterior cruciate ligament graft in a goat model. Am J Sports Med, 2001, 29(5): 620-626.
8. Cho S, Muneta T, Ito S, Y, et al. Electron microscopic evaluation of two-bundle anatomically reconstructed anterior cruciate ligament graft. J Orthop Sci, 2004, 9(3): 296-301.
9. Marumo K, Saito M, Yamagishi T, et al. The " Ligamentization” process in human anterior cruciate ligament reconstruction with autogenous patellar and hamstring tendons: a biochemical study. Am J Sports Med, 2005, 33(8): 1166-1173.
10. Cribb AM, Scott JE. Tendon response to tensile stress: an ultrastructural investigation of collagen: proteoglycan interactions in stressed tendon. J Anat, 1995, 187(Pt 2): 423-428.
11. Wells HC, Edmonds RL, Kirby N, et al. Collagen fibril diameter and leather strength. J Agric Food Chem, 2013, 61(47): 11524-11531.
12. Parry DA, Barnes GR, Craig AS. A comparison of the size distribution of collagen fibrils in connective tissues as a function of age and a possible relation between fibril size distribution and mechanical properties. Proc R Soc Lond B Biol Sci, 1978, 203(1152): 305-321.
13. Goodship AE, Birch HL, Wilson AM. The pathobiology and repair of tendon and ligament injury. Vet Clin North Am Equine Pract, 1994, 10(2): 323-349.
14. Anderson DM, Arredondo J, Hahn K, et al. Mohawk is a novel homeobox gene expressed in the developing mouse embryo. Dev Dyn, 2006, 235(3): 792-801.
15. Liu H, Liu W, Maltby KM, et al. Identification and developmental expression analysis of a novel homeobox gene closely linked to the mouse twirler mutation. Gene Expr Patterns, 2006, 6(6): 632-636.
16. 吴冰, 许美权, 李盛, 等. 关节镜下不同塑形状态前交叉韧带移植物 Mohawk 转录因子及胶原表达差异的研究. 中华创伤骨科杂志, 2018, 20(5): 529-536.
17. 吴冰, 陆伟, 王大平, 等. 前交叉韧带重建术后 MRI 评分与临床膝关节主、客观功能评分的对比研究. 中国临床解剖学杂志, 2016, 34(6): 677-684.
18. Kondo E, Yasuda K. Second-look arthroscopic evaluations of anatomic double-bundle anterior cruciate ligament reconstruction: relation with postoperative knee stability. Arthroscopy, 2007, 23(11): 1198-1209.
19. Lee JH, Bae DK, Song SJ, et al. Comparison of clinical results and second-look arthroscopy findings after arthroscopic anterior cruciate ligament reconstruction using 3 different types of grafts. Arthroscopy, 2010, 26(1): 41-49.
20. Zaffagnini S, De Pasquale V, Marchesini Reggiani L, et al. Electron microscopy of the remodelling process in hamstring tendon used as ACL graft. Knee Surg Sports Traumatol Arthrosc, 2010, 18(8): 1052-1058.
21. Abe S, Kurosaka M, Iguchi T, et al. Light and electron microscopic study of remodeling and maturation process in autogenous graft for anterior cruciate ligament reconstruction. Arthroscopy, 1993, 9(4): 394-405.
22. Sánchez M, Anitua E, Azofra J, et al. Ligamentization of tendon grafts treated with an endogenous preparation rich in growth factors: gross morphology and histology. Arthroscopy, 2010, 26(4): 470-480.
23. Rougraff B, Shelbourne KD, Gerth PK, et al. Arthroscopic and histologic analysis of human patellar tendon autografts used for anterior cruciate ligament reconstruction. Am J Sports Med, 1993, 21(2): 277-284.
24. Strocchi R, de Pasquale V, Gubellini P, et al. The human anterior cruciate ligament: histological and ultrastructural observations. J Anat, 1992, 180(Pt 3): 515-519.
25. Shino K, Oakes BW, Horibe S, et al. Collagen fibril populations in human anterior cruciate ligament allografts. Electron microscopic analysis. Am J Sports Med, 1995, 23(2): 203-209.
26. Frogameni AD, Jack son DW. Collagen remodelling in ACL reconstruction//The anterior cruciate ligament: current and future concepts. New York: Raven Press, 1993: 219-220.
27. Shino K, Oaes B, Inone M, et al. Human allografts collage fibril populations as a function of age of the graft. Trans Orthop Res Sco, 1990, 15(4): 520.
28. Shadwick RE. Elastic energy storage in tendons: mechanical differences related to function and age. J Appl Physiol (1985), 1990, 68(3): 1033-1040.
29. Jackson DW, Grood ES, Goldstein JD, et al. A comparison of patellar tendon autograft and allograft used for anterior cruciate ligament reconstruction in the goat model. Am J Sports Med, 1993, 21(2): 176-185.
30. Butler DL, Grood ES, Noyes FR, et al. On the interpretation of our anterior cruciate ligament data. Clin Orthop Relat Res, 1985, (196): 26-34.
31. Kennedy JC, Hawkins RJ, Willis RB, et al. Tension studies of human knee ligaments. Yield point, ultimate failure, and disruption of the cruciate and tibial collateral ligaments. J Bone Joint Surg (Am), 1976, 58(3): 350-355.
32. Dong S, Xie G, Zhang Y, et al. Ligamentization of autogenous hamstring grafts after anterior cruciate ligament reconstruction: midterm versus long-term results. Am J Sports Med, 2015, 43(8): 1908-1917.
33. 夏春, 张兵, 王少杰, 等. 前十字韧带重建术后自体 Hamstring 腱的超微结构研究. 中华骨科杂志, 2009, 29(3): 248-251.
34. Nakahara H, Hasegawa A, Otabe K, et al. Transcription factor Mohawk and the pathogenesis of human anterior cruciate ligament degradation. Arthritis Rheum, 2013, 65(8): 2081-2089.

Chinese Journal of Reparative and Reconstructive Surgery

A correlation study between the Mohawk expression level and the collagen fiber diameter of hamstring tendon graft after anterior cruciate ligament reconstruction

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