In vitro evaluation of low-intensity pulsed ultrasound in herniated disc resorption.

Herniated disc (HD) is often resolved spontaneously without surgical intervention. HD resorption (HDR) is associated with abundant vascularization and infiltration of macrophages (Mphi) into the intervertebral disc (ID), as well as with high levels of matrix metalloproteinases (MMPs). Low-intensity pulsed ultrasound (LIPUS) accelerates bone fracture healing in clinical studies, and angiogenic factors are involved in the mechanism of action. In the present study, we examined the effects of LIPUS on HDR in a rat in vitro HD model. HDR was enhanced by LIPUS as measured by the change in the wet weight of the cultured ID. The secretion of tumor necrosis factor-alpha (TNF-alpha) and macrophage chemoattractant protein-1 (MCP-1) from Mphi into the culture medium was stimulated by LIPUS. LIPUS also enhanced matrix metalloproteinase-3 (MMP-3) maturation. Moreover, many apoptotic cell death were observed in the HDR groups with LIPUS exposure. These results suggest that LIPUS enhanced the HDR via MMP-3 activation through TNF-alpha and MCP-1 pathways. Although animal studies and clinical trial are needed to understand the LIPUS effects on HDR, LIPUS treatment might be an effective treatment for accelerating HDR.

[1]  G. Vanhorn,et al.  Lumbar disc disease. , 1985 .

[2]  K. Furuya,et al.  The Natural History of Herniated Nucleus Pulposus With Radiculopathy , 1996, Spine.

[3]  J A Buckwalter,et al.  Articular cartilage and intervertebral disc proteoglycans differ in structure: An electron microscopic study , 1989, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[4]  T. Einhorn,et al.  Tumor necrosis factor alpha activation of the apoptotic cascade in murine articular chondrocytes is associated with the induction of metalloproteinases and specific pro-resorptive factors. , 2003, Arthritis and rheumatism.

[5]  S. Murakami,et al.  Chemonucleolysis With Human Stromelysin‐1 , 1997, Spine.

[6]  H. Haro,et al.  Vascular endothelial growth factor (VEGF)‐induced angiogenesis in herniated disc resorption , 2002, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[7]  M. Dyson,et al.  Effect of therapeutic ultrasound on the healing of full-thickness excised skin lesions. , 1990, Ultrasonics.

[8]  S. Hukuda,et al.  Immunohistochemical Study of Matrix Metalloproteinase‐3 and Tissue Inhibitor of Metalloproteinase‐1 in Human Intervertebral Discs , 1996, Spine.

[9]  Javad Parvizi,et al.  Calcium signaling is required for ultrasound‐stimulated aggrecan synthesis by rat chondrocytes , 2002, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[10]  M. Dyson,et al.  Macrophage responsiveness to therapeutic ultrasound. , 1990, Ultrasound in medicine & biology.

[11]  R. Marti,et al.  Low‐intensity ultrasound stimulates endochondral ossification in vitro , 2001, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[12]  David G. Borenstein Epidemiology, etiology, diagnostic evaluation, and treatment of low back pain , 1999 .

[13]  T. Ikeda,et al.  Enhanced leukotriene C4 synthase activity in thioglycollate-elicited peritoneal macrophages. , 1990, Biochemical and biophysical research communications.

[14]  T. Muneta,et al.  Sequential dynamics of monocyte chemotactic protein‐1 expression in herniated nucleus pulposus resorption , 1997, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[15]  T. Rytömaa,et al.  Platelet-derived growth factor and vascular endothelial growth factor expression in disc herniation tissue: an immunohistochemical study , 2005, European Spine Journal.

[16]  J. Damoiseaux,et al.  Rat macrophage lysosomal membrane antigen recognized by monoclonal antibody ED1. , 1994, Immunology.

[17]  J. Wark,et al.  Acceleration of Fresh Fracture Repair Using the Sonic Accelerated Fracture Healing System (SAFHS): A Review , 2000, Calcified Tissue International.

[18]  A. Gross,et al.  Autoimmunity in degenerative disc disease of the lumbar spine. , 1975, The Orthopedic clinics of North America.

[19]  A. Naylor,et al.  Enzymic and immunological activity in the intervertebral disk. , 1975, The Orthopedic clinics of North America.

[20]  Eric Hume,et al.  Power Doppler Assessment of Vascular Changes During Fracture Treatment With Low‐Intensity Ultrasound , 2003, Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine.

[21]  A. Newby,et al.  Role of Nuclear Factor-&kgr;B Activation in Metalloproteinase-1, -3, and -9 Secretion by Human Macrophages In Vitro and Rabbit Foam Cells Produced In Vivo , 2002, Arteriosclerosis, thrombosis, and vascular biology.

[22]  James D. Kang,et al.  Herniated Cervical Intervertebral Discs Spontaneously Produce Matrix Metalloproteinases, Nitric Oxide, Interleukin‐6, and Prostaglandin E2 , 1995, Spine.

[23]  C. Rubin,et al.  Enhancement of fracture healing by low intensity ultrasound. , 1998, Clinical orthopaedics and related research.

[24]  Y. Azuma,et al.  Effects of ultrasound and 1,25-dihydroxyvitamin D3 on growth factor secretion in co-cultures of osteoblasts and endothelial cells. , 2000, Ultrasound in medicine & biology.

[25]  K. Reinker,et al.  Cytokine mRNA repertoire of articular chondrocytes from arthritic patients, infants, and neonatal mice , 2005, Rheumatology International.

[26]  Javad Parvizi,et al.  Exposure to low‐intensity ultrasound increases aggrecan gene expression in a rat femur fracture model , 1996, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[27]  Y. Okada,et al.  A one-step sandwich enzyme immunoassay for human matrix metalloproteinase 3 (stromelysin-1) using monoclonal antibodies. , 1992, Clinica chimica acta; international journal of clinical chemistry.

[28]  W. Akeson,et al.  Proteoglycan chemistry of the intervertebral disks. , 1977, Clinical orthopaedics and related research.

[29]  James Melrose,et al.  Assessment of the cellular heterogeneity of the ovine intervertebral disc: comparison with synovial fibroblasts and articular chondrocytes , 2003, European Spine Journal.

[30]  T. Nishida Kinetics of tissue and serum matrix metalloproteinase-3 and tissue inhibitor of metalloproteinases-1 in intervertebral disc degeneration and disc herniation. , 1999, The Kurume medical journal.

[31]  B. Fingleton,et al.  Matrix metalloproteinase-3-dependent generation of a macrophage chemoattractant in a model of herniated disc resorption. , 2000, The Journal of clinical investigation.

[32]  S. Klahr,et al.  Angiotensin II receptor antagonist ameliorates renal tubulointerstitial fibrosis caused by unilateral ureteral obstruction. , 1995, Kidney international.

[33]  C. Perez,et al.  A novel form of TNF/cachectin is a cell surface cytotoxic transmembrane protein: Ramifications for the complex physiology of TNF , 1988, Cell.

[34]  A. Matsukawa,et al.  Expression of monocyte chemoattractant protein‐1 in primary cultures of rabbit intervertebral disc cells , 2002, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[35]  A J Bailey,et al.  Proceedings: Intervertebral disc collagen in degenerative disc disease. , 1975, Annals of the rheumatic diseases.

[36]  H. Iwata,et al.  The Involvement of Matrix Metalloproteinases and Inflammation in Lumbar Disc Herniation , 1998, Spine.

[37]  B. Fingleton,et al.  Matrix metalloproteinase-7-dependent release of tumor necrosis factor-alpha in a model of herniated disc resorption. , 2000, The Journal of clinical investigation.

[38]  D. Spengler,et al.  In vivo macrophage recruitment by murine intervertebral disc cells. , 2001, Journal of spinal disorders.