Name of Division: Orthopaedic Surgery

Staff

Education

　　Undergraduate Course

　　　

　　Graduate Course

　・Orthopaedic and Spinal Surgery

　・ Section of Orthopaedic Surgery Division of Bio-Matrix

　・ Rehabilitation

　

Research Subjects

　　　・Transplantation of embryonic neural stem cells (NSCs) into rat spinal cord

　Widespread distribution of transplanted NSCs (Fig. green) and their preferential differentiation into oligodendrocyte lineage suggest possible therapeutic application of this system for modification of spinal cord environment after injury.

　　　・Functional examination of spinal cord and peripheral nerve with SQUID magnetometer

　Neuromagnetic recording with SQUID (Super Conducting Quantum Interference Device) system is a developing technique, which is now generally used for examination of brain function as magnetoencephalography (MEG). Since magnetic field is not affected by the electrical conductivity of surrounding tissue, neuromagnetic recording has an advantage over the conventional electrophysiological examination and is expected to be a practical examination for neural function. The objects of our research are to develop a non-invasive functional examination in spinal cord and peripheral nerve using SQUID system, and to localize pathological nerve lesion accurately. In addition, neuromagnetic recording could allow spatial visualization of neural activity.

　　　・Analysis of the mechanisms of spontaneous resorption of herniated disc (HD) and Clinical application

　Herniated disc is a major cause of low back pain. MRI study has shown a spontaneous gradual decrease in the size of HD. We have determined that infiltrated macrophages and disc cells in HD tissues express the MMP-3 and MMP-7, which both play as a potent proteoglycanase, and VEGF (vascular endothelial growth factor) as a potent angiogenetic factor. Now, we are investigating the mechanisms how neovascularization and disc degradation occurs at the presence of macrophage in disc tissues in the resorption process of herniated disc.

・Elucidation of the molecular mechanisms of wear debris induced osteolysis.

　Orthopedic wear debris has been thought to be an important factor associated with osteolysis and loosening of total joint arthroplasties. We approach the molecular mechanisms of wear debris induced osteolysis to prevent loosening of implants

・Intrinsic Optical Imaging of Neural Activity of Spinal Cord -A New Method for Functional Imaging of Spinal Cord-

　Using intrinsic optical recording methods, we are studying the functional organization/architecture in the rat spinal cord, and making functional mapping of spinal cord. Intrinsic optical signal originates from secondary metabolic activities resulting from the neural activity, such as increasing deoxy-Hb, blood volume and shrinkage of neuron cell body, etc, that means this technique can provide higher spatial resolution compared with the previous functional imaging techniques such as PET or functional MRI. So this technique could be much more and more widely applicable for analyzing spinal cord function in near future.

・Bone regeneration by our material (Hydroxyapatite / Type�Tcollagen composite).

　Our research is to make the material which is replaced our own bone. We have prepared the material named HAp/Col (Hydroxyapatite / Type�Tcollagen) composite, aligning the hydroxyapatite nano-crystals along collagen molecules. At first, we evaluate the highly adsorptive potent of this, in vitro. And in vivo, we examin the biocompatibility, osteoconductive activity and efficacy as a carrier of proteins like rhBMP-2 of this novel biomaterial implanted in the weight-bearing site.

・Elucidation of the molecular mechanisms of wear debris induced osteolysis.

　Orthopedic wear debris has been thought to be an important factor associated with osteolysis and loosening of total joint arthroplasties. We approach the molecular mechanisms of wear debris induced osteolysis to prevent loosening of implants.

・The mechanism of oncogenesis in musculoskeletal sarcomas

　We analyze the relationship between oncogenesis in musculoskeletal systems and epigenetics, especially abnormalities of SWI/SNF complex and oncogenesis.

・Identification of novel genes expressing in chondrogenesis

　I am developping a unique gene trapping method to identify novel genes expressing in chondrogenesis using mouse embryonic cell line, ATDC5.

・The development of the intraarticular ligament and cartilage.

　We investigate gene expression in the development of intrarticular ligament and cartilage using chick and mouse embryo.

　

Publications

2001

　 1. Kazuyoshi Yagishita, Takeshi Muneta, Haruyasu Yamamoto, Kenichi Shinomiya. THE RELATIONSHIP BETWEEN POSTOPERATIVE LIGAMENT BALANCE AND PREOPERATIVE VARUS DEFORMITY IN TOTAL KNEE ARTHROPLASTY The Bulletin of Hospital for Joint Diseases Vol. 60(1), 23-28, 2001

　 2. Agnihotri R, Crawford HC, Haro H, Matrisian LM, Havrda MC, Liaw L. Osteopontin, a novel substrate for matrix metalloproteinase-3 (stromelysin-1) and matrix metalloproteinase-7 (matrilysin). J Biol Chem 2001 Jul 27;276 (30):28261-7

　 3. Kaar SG, Ragab AA, Kaye SJ, Kilic BA, Jinno T, Goldberg VM, Bi Y,Stewart MC, Carter JR, Greenfield EM Rapid repair of titanium particle-induced osteolysis is dramatically reduced in aged mice. J Orthop Res. 2001 Mar;19(2):171-8

　 4. Y. Wakabayashi, H. Komori, T. Kawa-uchi, K. Mochida, M.Takahashi, ML. Qi, K. Otake, K. Shinomiya Functional Recovery and Regeneration of Descending Tracts in Rats after Spinal Cord Transection in Infancy Spine 26(11) : 1215-1222, 2001

　 5. Y Asou Osteopontin facilitates angiogenesis, accumulation of osteoclasts, and resorption in ectopic bone.. Endocrinology. 142(3):1325-32, 2001

　 6. Y. Wakabayashi, H. Komori, T. Kawauchi, K. Mochida, M. Takahashi, M. Qi, K. Otake, K.Shinomiya Functional recovery and regeneration of descending tracts in rats after spinal cord transection in infancy. Spine 26:1215-1222, 2001

　 7. M. Takahashi, H. Haro, Y. Wakabayashi, T. Kawauchi, H. Komori, K. Shinomiya The assocoation of degeneration of the intervertebral disc with 5a/6a　polymorphism in the promotor of the human matrix metalloprotease-3 gene. JBJS85-B:491-495,2001

　 8. Matsuoka T, Yamaura I, Kurosa Y, Nakai O, Shindo S, Shinomiya K Long-term results of the anterior floating method for cervical myelopathy caused by ossification of the posterior longitudinal ligament. Spine 26:241-248, 2001

　 9. M Kikuchi, S Itoh, S Ichinose, K Shinomiya, J Tanaka Self-organization mechanism in a bone-like hydroxyapatite/collagen nanocomposite synthetized in vivo and its biological reaction in vivo. Biomaterials22: 1705-1711, 2001

　10. S. Itoh, M Matsubara, T Kawauchi, H Nakamura, S Yukitake, S Ichinose, K Shinomiya Enhancement of bone ingrowth in a titanium fiber mesh implant by rhBMP-2 and hyaluronic acid. J. of Material Science: Materials in Medicine12:575-581, 2001

　11. K Shinomiya, S Itoh, T Kawauchi, K Masanori, J Tanaka Development of a novel hydroxyapatite/collagen composite biomaterial. Tissue Engineering for Therapeutic Use 5:165-177, 2001

　12. H Nakamura, S Morita, Y Kumei, H Shimokawa, K Ohya, K Shinomiya Effect of Neurectomy and tenotomy on the bone mineral density and strength of tibiae. Acta Astronautica 49:179-190, 2001

　13. H.Asano, M.Matsubara, K Suzuki, S Morita, K Shinomiya Prevention of pulmonary embolism by a foot sole pump. Journal of Bone and Joint Surgery83-B:1130-1132, 2001

　14. K Shinomiya The relationship between ligament balance and postoperative varus deformity intotal knee arthroplasty. Bulletin,Hospital for Joint Diseases 60: 23-28, 2001

　15. I.Sekia, K.Tsuji, V Harley, Y Yamada, K Shinomiya, A Nifuji, M Noda Dexamethasone enhances SOX9 expression in chondrocytes. J.Endocrinology169:573-579, 2001

　16. Y Asou, S Rittling H Yoshitake, K Tsuji, K Shinomiya, A Nifiji, D Denhardt M Noda Osteopontin Facilitates angiogenesis, accumulation of osteoclasts, and Resorption in ectopic bone. Endocrinology 142:1325-1332, 2001

　17. S.Itoh, K Takakuda, S Ichinose, M Kikuchi, K Shinomiya A study of induction of nerve regeneration using bioabsorbable tubes. J of Reconstructive Microsurgery 17:115-123, 2001

　18. Asano H., Matsubara M., Suzuki K., Morita S., Shinomiya K Prevention of pulmonary embolism by a foot sole pump The Journal of Bone and Joint Surgery, 83-B: 1130-1132, 2001

2000

　 1. Haro H, Howard CC, Fingleton B, MacDougall JR, Shinomiya K, Spengler DM, Matrisian LM:Chondrocyte Matrix Metalloproteinase-3 is required for the Generation of a Macrophage Chemoattractant: Role in Macrophage Infiltration in a Coculture Model of Herniated Disc Resorption. J Clin.Invest.2000;105:133-141

　 2. Haro H, Howard CC, Fingleton B, Shinomiya K, Spengler DM, Matrisian LM: Matrix Metalloproteinase-7 is required for Tumor Necrosis Factor-a release from activated Macrophage: Role in Macrophage Infiltration in a Conculture Model of Herniated Disc Resorption. J Clin.Invest.2000;105:143-150

　 3. Itoh S, Kikuchi M, Koyama Y, Matsumoto H, Ichinose S, Tanaka J, Kawauchi T, Shinomiya K:The biocompatibility and Osteoconductive Activity of a Novel Hydroxyapatite/collagen Composite Biomaterial, and its Function as a Carrier of BMP2. J Biomedical Material Research 2000;52:445-453

　 4. Morita S, Yamamoto H, Hasegawa S, Kawachi S, Shinomiya K:Long-term Results of Valgus-extension Femoral Osteotomy for Advanced Osteoarthritis of the Hip. JBJS(B) 2000;82(6):824-829

　 5. Sakai T, Morita S, Shinomiya K, Watanabe A, Nakabayshi N, Ishihara K:Prevension of Fibrous Layer Formation Between Bone and Adhesive Bone Cement:in vivo evaluation of bone impregnation with 4-META/MMA-TBB cement. J Biomedical Material Research 2000;52(1):24-29

　 6. Sekiya I, Tsuji K, Koopman P, Watanabe H, Yamada Y, Shinomiya K, Nifuji A, Noda M:SOX9 Enhances Aggrecan Gene Promotor/enhancer Activity and is Upregulated by Retinoic Acid in a Cartilage-derived Cell Line, TC6. J Biological Chemistry 2000;275(15):10738-44

　 7. Abe M, Tsuchiya K, Kurosa Y, Nakai O, Shinomiya K:Multiple Sclerosis with Very Late Onset. J Spinal Disorder 2000;13:545-549

　 8. Shinomiya K, Itoh S, Kawauchi T, Kikuchi M, Tanaka J:Development of a Novel Hydroxyapatite/collagen Composite Biomaterial. Tissue Engineering for Therapeutic Use, Elsevier 2000;5:165-177

1999

　 1.　Muneta T, Sekiya I, Tsuchiya M, Yamamoto H, Shinomiya:K: A technique for reconstruction of the medial patellofemoral ligament. Clin Orthop.1999;359:151-155

　 2.　Muneta T, Sekiya I, Yagishita K, Ogiuchi T, Yamamoto H, Shinomiya K: Two-bundle reconstruction of the anterior cruciate ligament using semitendinosus tendon with Endobuttons: Operative technique and preliminary results. Arthroscopy.1999;15:613-617

　 3.　Muneta T, Yagishita K, Kurihara Y, Sekiya I: Intra-articular detachment of the Endobutton more than 18 months after anterior cruciate ligament reconstruction. Arthroscopy.1999;15: 775-778 　

　 4.　Morita S, Kawachi S, Yamamoto H, Shinomiya K, Nakabayashi N, Ishihara K: Total hip arthropasty using bone cement containing tri-n-butylborane as the initiator. J Biomed Mater Res.1999;48:759-763　

　 5.　Matsubara M, Nakamura K, Morita S, Kashima I:Non-invasive assessment of bone quality. J Med Dent Sci.1999;46(4):1-12

　 6.　Itoh S, Muneta T, Shinomiya K, Ichinose S:Electron Microscopic Evaluation for the Effects of Stress-shielding on Maturation of the Mid-substance and Ligament-bone Junction of the Reconstructed Anterior Cruciate ligament in Rabbits. J Materials Science.1999;10 (3):185-190

　 7.　Itoh S, Takakuda K, Samejima H, Shinomiya K, Ichinose S:Synthetic collagen fibers coated with a synthetic peptide containing the YIGSR sequence of laminin promote peripheral nerve regeneration in vivo. J Materials Science. 1999;10 (3):129-134

　 8.　Itoh S, Samejima H, Shinomiya K, Awaya A:The effect of neurotrophic pyrimidine heterocyclic compounds, MS-818 and MS-430, on the regeneration of injured peripheral nerves. Restorative Neurology and Neuroscience. 1999;14:265-273

　 9.　Itoh S, Ohta G, Samejima H, Shinomiya K:Bone mineral density in the distal radius in a healthy Japanese population and in relation to fractures of the distal radius. J Hand Surg. 1999;24-B:334-337

　10.　Abe M, Yoshioka K, Shinomiya K, Nakai O: Drug sensitivities of the primary afferents and their changes after inflammation. Clin Orthop.1999;369:340-348

　11.　Abe M, Komori H, Yamaura I, Kayano T: Spinal cord herniation into an extensive extradural meningeal cyst: postoperative analysis of intracystic flow by phase-contrast cine MRI. J Orthop Sci.1999;4:450-456

　12.　Mimori K, Muneta T, Komori H, Okawa A, Shinomiya K: Relationship Between the Painful Shoulder and the Cervical Spine with Narrow Canal in Patients without Obvious Radiculopathy. J Shoulder Elbow Surg.1999;8(4):303-306.

　13.　Mimori K, Muneta T, Nakagawa T, Shinomiya K: A New Pain Provocation Test for Superior Labral Tears of the Shoulder.Am J Sports Med. 1999;27:137-142

　14.　Ikeda H , Muneta T , Niga S , Hoshino A , Asahina S , Yamamoto H : The Long-term Effects of Tibial Drill Hole Position on the Outcome of Anterior Cruciate Ligament Reconstruction. Arthroscopy 15:287-291, 1999

　15.　Nakamura K, Matsubara M, Kashima I:Mathematical morphology for extraction of bone travecular pattern. J Jpn Soc Bone Morphom. 1999;9:45-51

　16.　Arai Y, Momose-Sato Y, Sato K, Kamino K :Optical mapping of neural network activity in the chick spinal cord at an intermediate stage of embryonic development. Journal of Neurophysiology.1999;81(4):1889-1902

1997

　　1.　Ezura Y, Tournay O, Noda M: A novel negative vitamin D response sequence in the promoter of Id1: An inhibitory transcription factor in osteoblastic　differentiation. Trans Orthop Res Soc, 22: 326, 1997.

　　2.　Haro H, Komori H, Okawa A, et al: Sequential dynamics of Monocyte Chemotactic Protein-1 expression in　herniated nucleus pulposus resorption. JOR, 15: 734-741, 1997.

　　3.　Haro H, Murakami S, Komori H, et al: Chemonucleolysis with human Stromelysin-1. Spine, 22: 1098-1104, 1997.

　　4.　Itoh S, Shinomiya K, Samejima H, et al: An experimental study on nerve regeneration through the basement membrane tubes of the nerve, muscle, and artery. Microsurgery, 17: 525-534, 1997.

　　5.　Morita S, Yamamoto H, Furuya K, et al: Enhanced strength in cemented stem fixation using adhesive acrylic cement as a metal coating material. Journal of Biomedical Material Research, 34: 171-175, 1997.

　　6.　Ezura Y, Tournay O, Nifuji A, et al: Identification of a novelsuppressive vitamin D response sequence in the 5' flanking region of murine Id1 gene. Journal of Biological Chemistry, 272: 29865-29872, 1997.

　　7.　Muneta T, Takakuda K, Yamamoto H: Intercondylar notch width and its relation to the configuration and cross-sectional area of the anterior cruciate ligament. A cadaveric knee study. Am J Sports Med 1997;25:69-72.

　　8.　Murakami S, McMahon AP, Noda M: Indian hedgehog gene is expressed in osteoblasts and is regulated by TGF-b. Trans Orthop Res Soc, 22: 327, 1997.

　　9.　Murakami S, Nifuji A, Noda M: Expression of indian hedgehog in osteoblasts and its posttranscriptional regulation by Transforming Growth Factor-b. Endocrinology, 138: 1972-1978, 1997.

　 10.　Murakami S, Muneta T, Ezura Y, et al: Quantitative analysis of synovial fibrosis in the infrapatellar fat pad. Before and after anterior cruciate ligament reconstruction. Am J Sports Med, 25: 29-34, 1997.

　 11.　Mochida K, Komori H, Okawa A, et al: Evaluation of motor function during thracic and thoracolumbar spinal surgery based on MEP using train spinal stimulation. Spine, 22:1385-93, 1997.

　 12.　Kawa-uchi T, Olson E, Mataga N, et al: A basic helix-loop-helix transcription factor, scleraxis, is expressed in chondrocytes and is suppressed by FGF. Trans Orthop Res Soc, 22: 342, 1997.

　 13.　Komori H, Okawa A, Haro H, et al: Contrast-enhanced magnetic resonance imaging in conservative management of lumbar disc herniation. Spine, 23: 67-73, 1997

　

[Graduate School, School of Medicine]

［TOKYO MEDICAL AND DENTAL UNIVERSITY］