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Low energy extracorporeal shock wave therapy combined with low tension traction can better reshape the microenvironment in degenerated intervertebral disc regeneration and repair
Authors:Yan-Jun Che  Jun-Jun Hou  Jiang-Bo Guo  Ting Liang  Wen Zhang  Yan Lu  Hui-Lin Yang  Yue Feng Hao  Zong-Ping Luo
Institution:1. Orthopaedic Institute, Department of Orthopaedics, The First Affiliated Hospital of SooChow University, 708 Renmin Rd, Suzhou, Jiangsu 215007, People''s Republic of China;2. Department of Orthopedics, Heping Hospital Affiliated to Changzhi Medical College, Changzhi, Shanxi, People''s Republic of China;3. Department of Geriatrics, Xinghu Hospital, SuZhou industrial park, Suzhou, Jiangsu, People''s Republic of China;4. Department of Endocrinology, The First Affiliated Hospital of SooChow University, Suzhou, Jiangsu, People''s Republic of China;5. Orthopedics and Sports medicine center, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou 215000, Jiangsu, People''s Republic of China;1. Department of Orthopaedic Surgery, Center for Musculoskeletal Research, Department of Physical Medicine and Rehabilitation, Vanderbilt University Medical Center, 1215 21st Ave South, Medical Center East–South Tower, Suite 4200, Nashville, TN 37232, USA;2. Department of Orthopaedic Surgery, Vanderbilt University Medical Center, 1215 21st Ave South, Medical Center East–South Tower, Suite 4200, Nashville, TN 37232, USA;3. Department of Orthopaedic Surgery, Center for Musculoskeletal Research, Vanderbilt University Medical Center, 1215 21st Ave South, Medical Center East–South Tower, Suite 4200, Nashville, TN 37232, USA;4. Department of Orthopaedic Surgery, Johns Hopkins University, 601 N. Caroline St, Baltimore, MD 21287, USA;5. Department of Neurological Surgery, University of Cincinnati College of Medicine, 222 Piedmont Ave, Suite 2200, Cincinnati, OH 45219, USA;6. Howell Allen Clinic, Saint Thomas Medical Partners, 2011 Murphy Ave, Suite 301, Nashville, TN 37203, USA;7. Steamboat Orthopaedic and Spine Institute, 904 Central Park Drive, Suite 280, Steamboat Springs, CO 80487, USA;8. Department of Physical Medicine and Rehabilitation, Johns Hopkins University, 601 N. Caroline St, Baltimore, MD 21287, USA;9. Department of Orthopaedic Surgery, Center for Musculoskeletal Research, Department of Physical Medicine and Rehabilitation, Osher Center for Integrative Medicine, Vanderbilt University Medical Center, 1215 21st Ave South, Medical Center East–South Tower, Suite 4200, Nashville, TN 37232, USA;1. Department of Orthopaedics, Icahn School of Medicine at Mount Sinai, The Mount Sinai Hospital, Massachusetts General Hospital, 55 Fruit St, Boston, MA 02114, USA;2. Department of Orthopaedics, Harvard Medical School, Massachusetts General Hospital, 55 Fruit St, Boston, MA 02114, USA;3. Department of Orthopaedics, Maimonides Bone and Joint Center, Maimonides Medical Center, 6010 Bay Pkwy, Brooklyn, NY 11204, USA;4. Department of Orthopaedics, Icahn School of Medicine at Mount Sinai, The Mount Sinai Hospital, 5 East 98th St, New York, NY 10029, USA;1. Department of Orthopaedic Surgery, University Medical Center Utrecht, Utrecht, the Netherlands;2. Division of Orthopaedic Surgery, The Children''s Hospital of Philadelphia (CHOP), Philadelphia, PA, USA;1. Department of Orthopedic Surgery, MGH/BWH Orthopedic Spine Surgery Fellowship Program, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA;2. Department of Orthopedic Surgery, Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA;3. The Spine Journal, North American Spine Society, 7075 Veterans Boulevard, Burr Ridge, IL 60527, USA;1. Division of Infection, Department of Pediatrics, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Republic of Korea;2. Spine Center, Department of Orthopedics, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, 22, Gwanpyeong-ro, 170beon-gil, Dongan-gu, Anyang-si, Gyeonggi-do 14068, Republic of Korea
Abstract:BACKGROUNDLow-tension traction is more effective than high-tension traction in restoring the height and rehydration of a degenerated disc and to some extent the bony endplate. This might better reshape the microenvironment for disc regeneration and repair. However, the repair of the combination of endplate sclerosis, osteophyte formation, and even collapse leading to partial or nearly complete occlusion of the nutrient channel is greatly limited.PURPOSETo evaluate the effectiveness of low-intensity extracorporeal shock wave therapy (ESWT) combined with low tension traction for regeneration and repair of moderately and severely degenerated discs; to explore the possible mechanism of action.STUDY DESIGNAnimal study of a rat model of degenerated discs.METHODSA total of thirty-five 6-month old male Sprague-Dawley rats were randomly assigned to one of five groups (n=7, each group). In Group A (model group), caudal vertebrae were immobilized using a custom-made external device to fix four caudal vertebrae (Co7–Co10) whereas Co8–Co9 underwent 4 weeks of compression to induce moderate disc degeneration. In Group B (experimental control group), as in Group A, disc degeneration was successfully induced after which the fixed device was removed for 8 weeks of self-recovery. The remaining three groups of rats represented the intervention Groups (C–E): after successful generation of disc degeneration in Group C (com - 4w/tra - 4w) and Group D (com - 4w/ESWT), as described for group A, low-tension traction (in-situ traction) or low-energy ESWT was administered for 4 weeks (ESWT parameters: intensity: 0.15 Mpa; frequency: 1 Hz; impact: 1,000 each time; once/week, 4 times in total); Group E (com - 4w/tra - 4w/ESWT): disc degeneration as described for group A, low-tension traction combined with low-energy ESWT was conducted (ESWT parameters as Group D). After experimentation, caudal vertebrae were harvested and disc height, T2 signal intensity, disc morphology, total glycosaminoglycan (GAG) content, gene expression, structure of the Co8–Co9 bony endplates and elastic moduli of the discs were measured.RESULTSAfter continuous low-tension traction, low energy ESWT intervention or combined intervention, the degenerated discs effectively recovered their height and became rehydrated. However, the response in Group D was weaker than in the other intervention groups in terms of restoration of intervertebral disc (IVD) height, whereas Group E was superior in disc rehydration. Tissue regeneration was evident in Groups C to E using different interventions. No apparent tissue regeneration was observed in the experimental control group (Group B). The histological scores of the three intervention groups (Groups C–E) were lower than those of Groups A or B (p<.0001), and the scores of Groups C and E were significantly lower than those of Group D (p<.05), but not Group C versus Group E (p>.05). Compared with the intervention groups (Groups C–E), total GAG content of the nucleus pulposus (NP) in Group B did not increase significantly (p>.05). There was also no significant difference in the total GAG content between Groups A and B (p>.05). Of the three intervention groups, the recovery of NP GAG content was greatest in Group E. The expression of collagen I and II, and aggrecan in the annulus fibrosus (AF) was up-regulated (p<.05), whereas the expression of MMP-3, MMP-13, and ADAMTS-4 was down-regulated (p<.05). Of the groups, Group E displayed the greatest degree of regulation. The trend in regulation of gene expression in the NP was essentially consistent with that of the AF, of which Group E was the greatest. In the intervention groups (Groups C–E), compared with Group A, the pore structure of the bony endplate displayed clear changes. The number of pores in the endplate in Groups C to E was significantly higher than in Group A (p<.0001), among which Group C versus Group D (p=.9724), and Group C versus Group E (p=.0116). There was no significant difference between Groups A and B (p=.5261). In addition, the pore diameter also increased, the trend essentially the same as that of pore density. There was no significant difference between the three intervention groups (p=.7213). It is worth noting that, compared with Groups A and B, peripheral pore density and size in Groups D and E of the three intervention groups recovered significantly. The elastic modulus and diameter of collagen fibers in the AF and NP varied with the type of intervention. Low tension traction combined with ESWT resulted in the greatest impact on the diameter and modulus of collagen fibers.CONCLUSIONSLow energy ESWT combined with low tension traction provided a more stable intervertebral environment for the regeneration and repair of moderate and severe degenerative discs. Low energy ESWT promoted the regeneration of disc matrix by reducing MMP-3, MMP-13, and ADAMTS-4 resulting in inhibition of collagen degradation. Although axial traction promoted the recovery of height and rehydration of the IVD, combined with low energy ESWT, the micro-nano structure of the bony endplate underwent positive reconstruction, tension in the annulus of the AF and nuclear stress of the NP declined, and the biomechanical microenvironment required for IVD regeneration and repair was reshaped.
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