Effect of low-dose irradiation on structural and mechanical properties of hyaline cartilage-like fibrocartilage

Amaç: Bu çalışmanın amacı düşük doz X ışınının fibröz kıkırdak üzerindeki etkilerini araştırmak ve hiyalin kıkırdak ile aynı mekanik ve yapısal özelliklere sahip hiyalin kıkırdak benzeri fibrokıkırdak (HKBF) geliştirmek idi. Çalışma planı: Yirmi tavşanın 40 diz ekleminde osteokondral defekt oluşturuldu. Ameliyat sonrası 7. günde başlanarak her tavşanın tek bir dizine, 5 gün boyunca, günlük 1.0 Gy'lik dozlarla toplam 5.0 Gy X ışını uygulanırken (radyoterapi grubu), diğer dizi uygulama dışı bırakıldı (kontrol grubu). Tavşanlar daha sonra her birinde 5 adet olacak şekilde 4 gruba ayrıldı. İlk üç grup, sırasıyla, 4., 8. ve 12. haftada sakrifiye edildi ve kıkırdak defektleri makroskopik ve mikroskobik olarak incelendi. Kalan 5 tavşanın oluşturduğu grup da 12. haftada sakrifiye edilerek kıkırdak defektlerine biyomekanik sıkıştırma testleri uygulandı. Bulgular: Radyoterapi ve kontrol grupları arasında biyomekanik açıdan anlamlı bir fark saptanmadı (p=0.686). Yine, gruplar arasında makroskopik ve mikroskopik açıdan da anlamlı bir fark yoktu (p=0.300). Işınlanan grupta kondrosit kümelenmesi gözlendi. Çıkarımlar: Düşük doz X ışını HKBF dokusunun mekanik özelliklerini in vivo etkilememekle birlikte, kondrosit kümelenmesi gibi yapısal değişikliklere yol açmaktadır.

Düşük doz X ışınının hiyalin kıkırdak benzeri fibrokıkırdağın yapısal ve mekanik özellikleri üstündeki etkisi

Objective: The aim of this study was to analyze the effect of low-dose irradiation on fibrous cartilage and to obtain a hyaline cartilage-like fibrocartilage (HCLF) with similar structural and mechanical properties to hyaline cartilage. Methods: An osteochondral defect was created in 40 knees of 20 rabbits. At the 7th postoperative day, a single knee of each rabbit was irradiated with a total dose of 5.0 Gy in 1.0 Gy fractions for 5 days (radiotherapy group), while the other knee was not irradiated (control group). Rabbits were then divided into four groups of 5 rabbits each. The first three groups were sacrificed at the 4th, 8th and the 12th postoperative weeks and cartilage defects were macroscopically and microscopically evaluated. The remaining group of 5 rabbits was sacrificed at the 12th week and biomechanical compression tests were performed on the cartilage defects. Results: There was no significant biomechanical difference between the radiotherapy and the control group (p=0.686). There was no significant macroscopic and microscopic difference between groups (p=0.300). Chondrocyte clustering was observed in the irradiated group. Conclusion: Low-dose irradiation does not affect the mechanical properties of HCLF in vivo. However, structural changes such as chondrocyte clustering were observed.

___

1. Mankin HJ, Mow VC, Buckwalter JA. Articular cartilage repair and osteoarthritis. In: Buckwalter JA, Einhorn TA, Simon SR, editors. Orthopaedic basic science. Biology and biomechanics of the musculoskeletal system. 2nd ed. Rosemont, Illinois: American Academy of Orthopaedic Surgeons; 2000. p. 471-88.
2. Buckwalter JA. Evaluating methods of restoring cartilagi- nous articular surfaces. Clin Orthop Relat Res 1999;(367 Suppl):S224-38.
3. Mankin HJ. The response of articular cartilage to mechani- cal injury. J Bone Joint Surg Am 1982;64:460-6.
4. Buckwalter JA, Coutts R, Hunziker E, Van Mow C. Breakout Session 3: Articular cartilage. Clin Orthop Relat Res 1999;(367 Suppl):239-43.
5. Gross AE. Repair of cartilage defects in the knee. J Knee Surg 2002;15:167-9.
6. Shapiro F, Koide S, Glimcher MJ. Cell origin and differen- tiation in the repair of full-thickness defects of articular car- tilage. J Bone Joint Surg Am 1993;75:532-53.
7. Buckwalter JA, Lohmander S. Operative treatment of osteoarthrosis. Current practice and future development. J Bone Joint Surg Am 1994;76:1405-18.
8. Johnstone B, Yoo JU. Autologous mesenchymal progenitor cells in articular cartilage repair. Clin Orthop Relat Res 1999;(367 Suppl):S156-62.
9. Ochi M. Challenging for cartilage repair. Sports Med Arthrosc Rehabil Ther Technol 2009;1:13.
10. Fajardo LF. Morphology of radiation effects on normal tissue. In: Perez CA, Brady LW, editors. Principles and practice of radiation oncology. 3rd ed. Philadelphia: Lipincott-Raven; 1997. P. 143-54.
11. Shi CM, Su YP, Cheng TM. Recent advances in the patho- logical basis and experimental management of impaired wound healing due to total-body irradiation. Med Sci Monit 2006;12:RA1-4.
12. Takahashi S, Sugimoto M, Kotoura Y, Oka M, Sasai K, Abe M, et al. Long-lasting tolerance of articular cartilage after experimental intraoperative radiation in rabbits. Clin Orthop Relat Res 1992;(275):300-5.
13. Eng TY, Boersma MK, Fuller CD, Luh JY, Siddiqi A, Wang S, et al. The role of radiation therapy in benign diseases. Hematol Oncol Clin North Am 2006;20:523-57.
14. Wakitani S, Goto T, Pineda SJ, Young RG, Mansour JM, Caplan AI, et al. Mesenchymal cell-based repair of large, full-thickness defects of articular cartilage. J Bone Joint Surg Am 1994;76:579-92.
15. Liebmann A, Hindemith M, Jahns J, Madaj-Sterba P, Weisheit S, Kamprad F, et al. Low-dose X-irradiation of adjuvant-induced arthritis in rats. Efficacy of different frac- tionation schedules. Strahlenther Onkol 2004;180:165-72.
16. Fischer U, Kamprad F, Koch F, Ludewig E, Melzer R, Hildebrandt G. The effects of low-dose Co-60 irradiation on the course of aseptic arthritis in a rabbit knee joint. [Article in German] Strahlenther Onkol 1998;174:633-9.
17. Song SU, Hong YJ, Oh IS, Yi Y, Choi KB, Lee JW, et al. Regeneration of hyaline articular cartilage with irradiated transforming growth factor beta1-producing fibroblasts. Tissue Eng 2004;10:665-72.
18. O’Driscoll SW, Keeley FW, Salter RB. The chondrogenic potential of free autogenous periosteal grafts for biological resurfacing of major full-thickness defects in joint surfaces under the influence of continuous passive motion. An exper- imental investigation in the rabbit. J Bone Joint Surg Am 1986;68:1017-35.
19. O’Driscoll SW, Keeley FW, Salter RB. Durability of regen- erated articular cartilage produced by free autogenous periosteal grafts in major full-thickness defects in joint sur- faces under the influence of continuous passive motion. A follow-up report at one year. J Bone Joint Surg Am 1998;70: 595-606.
20. Mainil-Varlet P, Aigner T, Brittberg M, Bullough P, Hollander A, Hunziker E, et al. Histological assessment of cartilage repair: a report by the Histology Endpoint Committee of the International Cartilage Repair Society (ICRS). J Bone Joint Surg Am 2003;85-A Suppl 2:45-57.
21. Hangody L, Feczkó P, Bartha L, Bodó G, Kish G. Mosaicplasty for the treatment of articular defects of the knee and ankle. Clin Orthop Relat Res 2001;(391 Suppl):S328-36.
22. Horas U, Pelinkovic D, Herr G, Aigner T, Schnettler R. Autologous chondrocyte implantation and osteochondral cylinder transplantation in cartilage repair of the knee joint. A prospective, comparative trial. J Bone Joint Surg Am 2003; 85:185-92.
23. Poole AR. What type of cartilage repair are we attempting to attain? J Bone Joint Surg Am 2003;85:40-4.
24. Schultze J, Eilf K. Perspectives of radiation therapy in benign diseases. [Article in German] Strahlenther Onkol 2006;182:259-62.
25. Takahashi T, Mizobuchi H, Toda M, Maeda A, Mizuno S, Ogawa Y, et al. Metabolic effects of X-ray irradiation on adult human articular chondrocytes. Int J Mol Med 2003;11:631-4.
26. Hildebrandt G, Jahns J, Hindemith M, Spranger S, Sack U, Kinne RW, et al. Effects of low dose radiation therapy on adjuvant induced arthritis in rats. Int J Radiat Biol 2000;76:1143-53.
27. Hildebrandt G, Radlingmayr A, Rosenthal S, Rothe R, Jahns J, Hindemith M, et al. Low-dose radiotherapy (LD-RT) and the modulation of iNOS expression in adjuvant-induced arthritis in rats. Int J Radiat Biol 2003;79:993-1001.
28. Ailland J, Kampen WU, Schünke M, Trentmann J, Kurz B. Beta irradiation decreases collagen type II synthesis and increases nitric oxide production and cell death in articular chondrocytes. Ann Rheum Dis 2003;62:1054-60.
29. Mäkelä OT, Lammi MJ, Uusitalo H, Hyttinen MM, Vuorio E, Helminen HJ, et al. Analysis of lapine cartilage matrix after radiosynovectomy with holmium-166 ferric hydroxide macroaggregate. Ann Rheum Dis 2003;62:43-9.
30. Wang SJ, Lin WY, Chen MN, Chen JT, Ho WL, Hsieh BT, et al. Histologic study of effects of radiation synovecto- my with Rhenium-188 microsphere. Nucl Med Biol 2001;28:727-32.
31. Messner K. Hydroxylapatite supported Dacron plugs for repair of isolated full-thickness osteochondral defects of the rabbit femoral condyle: mechanical and histological evalua- tions from 6-48 weeks. J Biomed Mater Res 1993;27:1527- 32.
32. Nam EK, Makhsous M, Koh J, Bowen M, Nuber G, Zhang LQ. Biomechanical and histological evaluation of osteo- chondral transplantation in a rabbit model. Am J Sports Med 2004;32:308-16.
33. Reinholz GG, Lu L, Saris DB, Yaszemski MJ, O'Driscoll SW. Animal models for cartilage reconstruction. Biomaterials 2004;25:1511-21.
34. Hunziker EB. Biologic repair of articular cartilage. Defect models in experimental animals and matrix requirements. Clin Orthop Relat Res 1999;(367 Suppl):S135-46.
35. Lotz M. Cytokines in cartilage injury and repair. Clin Orthop Relat Res 2001;(391 Suppl):S108-15.
36. Margulies BS, Horton JA, Wang Y, Damron TA, Allen MJ. Effects of radiation therapy on chondrocytes in vitro. Calcif Tissue Int 2006;78:302-13.
37. Perka C, Schultz O, Spitzer RS, Lindenhayn K. The influ- ence of transforming growth factor beta1 on mesenchymal cell repair of full-thickness cartilage defects. J Biomed Mater Res 2000;52:543-52.
38. Kajiwara R, Ishida O, Kawasaki K, Adachi N, Yasunaga Y, Ochi M. Effective repair of a fresh osteochondral defect in the rabbit knee joint by articulated joint distraction follow- ing subchondral drilling. J Orthop Res 2005;23:909-15.
39. Kumagai K, Saito T, Koshino T. Articular cartilage repair of rabbit chondral defect: promoted by creation of periarticular bony defect. J Orthop Sci 2003;8:700-6.
40. Harada Y, Tomita N, Nakajima M, Ikeuchi K, Wakitani S. Effect of low loading and joint immobilization for sponta- neous repair of osteochondral defect in the knees of weight- less (tail suspension) rats. J Orthop Sci 2005;10:508-14.
41. Wei X, Gao J, Messner K. Maturation-dependent repair of untreated osteochondral defects in the rabbit knee joint. J Biomed Mater Res 1997;34:63-72.