重症型顎関節症に対する関節円板切除・耳介軟骨移植に関する研究

取得学位 : 博士（医学）, 学位授与番号 : 医博乙第1360号, 学位授与年月日：平成7年11月15日,学位授与年：199

顎関節症進行のメカニズムに関する研究

金沢大学附属病院1.うさぎ顎関節症モデルにおける組織変化時の酵素活性の観察うさぎ顎関節症モデルを用いて、基質分解酵素の発現を観察した。うさぎ関節円板の牽引により発生する顎関節の破壊時には、マトリックスメタロプロテアーゼ(MMP)やアグリカナーゼ(ADAMTS)などの発現がみられた。この発現は破壊が進行する期間を通じて認められ、牽引を解除することにより発生する修復の境界時期においても認められた。うさぎの顎関節においては、破壊と修復の期間を通して基質分解酵素の発現がみられるものと考えられた。また、下顎頭軟骨層においてはI型ならびにII型コラーゲンの発現が認められ、破壊の進行によりその比率に変化がみられた。2.臨床材料の検討外科療法が適応となった顎関節症患者からインフォームドコンセントを得て採取した滑液や線維性癒着組織の組織学的あるいは生化学的分析を行った。顎関節症が進行して画像所見にて変形性関節症変化が強く認められる症例では高頻度にMMPやADAMTSの発現が認められた。整形外科領域からは、軟骨の破壊時にADAMTSの発現によりプロテオグリカンが選択的に破壊されてからMMPが発現し、コラーゲンとプロテオグリカンの両者が破壊されると報告されている。しかし、我々が行った顎関節での研究ではADAMTSとMMPが同時に発現することが認められた。したがって、顎関節症における組織変化や破壊の進行度は整形外科領域の関節症と比べると軽度であると考えられた。また、鏡視下手術によって得られた関節腔における線維性癒着は細胞成分が豊富であり、関節円板穿孔症例では骨化や軟骨変性を伴うものが認められた。これらは術前のMRIで特徴的なものも含まれた。1. Experimental study of temporomandibular joint arthritis in the rabbitsProteolytic activities of the temporomandibular arthritis have been investigated using a rabbit model of temporomandibular disorders. Histopathologic examination has been achieved on the arthritis caused by an artificial dislocation of the articular disc. Throughout the examination period, histoimmunochemical staining showed expression of proteolytic enzymes such as matrix metalloproteinases (MMPs) and aggrecanase(ADAMTS). Especially in the critical destructive period, specimens showed higher incidence of enzymatic expression. Expression of type I and H collagen stain were also noticed in the cartilage layer of the mandibular condyle. Distribution of these components differed according to the destruction periods.2. Analyses of the clinically harvested materialsHistopatholigic and biochemistric examination have been carried out using human materials of synovial fluid and biopsy tissue from the upper joint compartment of the temporomandibular joints, under informed consent. In patients with prominent arthritic changes on Milk showed higher incidence of MMP5 and ADAMTS. During cartilage matrix destruction, ADAMTS first acts on proteoglycan breakdown, then MMPs act on proteoglycan and collagen breakdown. These enzymatic expressions have been noticed in RA patients in the field of Orthopedic Surgery. Conversely in the present study, high incidence of both enzymatic activities has been noticed in the temporomandibular joints. From the results, arthritis may be mild in the temporomandibular joints. Harvested adhesion tissue via arthroscopic surgery showed a number of fibro-blastic cells. Specimens from advanced stage of arthritis showed ossification or cartilaginous degeneration. These lesions are frequently showed in preoperative MRI images.研究課題/領域番号:17592069, 研究期間(年度):2005-2007出典：研究課題「顎関節症進行のメカニズムに関する研究」課題番号17592069（KAKEN：科学研究費助成事業データベース（国立情報学研究所）） （https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-17592069/175920692007kenkyu_seika_hokoku_gaiyo/）を加工して作

実験的顎関節症モデルに対する組織学的、生化学的研究

金沢大学附属病院初年度にウサギ変形性顎関節症モデルを確立し,顎関節円板の転位が関節円板の破壊と変形性顎関節症進行の要因であることを確認した。第2年度には,このモデルに対して臨床的に行われる関節円板整位術を施行した。その結果,関節円板整位術を早期に行った場合,顎関節構成組織の修復と再生,正常関節機能の保持が観察された。しかし,整位術を一次手術後3週目以降に行ったものでも,変形性顎関節症の進行と関節円板の破壊は二次手術を行わなかった場合と同じであり,関節円板整位術の適応限界が示された。現在,この破壊と修復過程に関する酵素活性の影響について免疫組織化学染色標本による検討を行っている。また第3年度からは,変形性顎関節症の原因の一つである下顎頭関節突起の外傷に関する実験的検討を行ってきた。週齢の異なるウサギ顎関節突起に転位脱臼骨折を起こし,骨折の程度と年齢が修復に与える影響に対して検討を行った。その結果,幼若期のウサギにおける関節突起骨折は変位の程度に関わらず,顎関節形態はほぼ完全に修復されることが示された。一方,成熟期のウサギでは変位の小さい骨折の場合は,ほぼ完全な修復がみられたが,転位脱臼骨折の場合,修復は不完全で顎関節形態の完全な回復は認めなかった。このことより,臨床で高頻度に遭遇する変位を伴う成人の下顎頭関節突起骨折では,積極的な観血的整復固定術の適用が示唆された。この修復過程における酵素活性の影響に関しても免疫組織化学染色標本を用いて継続して研究を行っていく予定である。Anterior disk displacement was induced in the craniomandibular joint of the rabbits. A sutured thread was placed at the antero-lateral margin of retrodiscal tissue and fixed to infra-orbital portion of zygoma after 7mm anterior displacement of the disk. Postoperative changes were assessed at the 2nd, 3rd, 5th, 8th, and 24th week. Disk displacement induced hypertrophy of articular cartilage of the condyle at the 2nd and 3rd week, then developed disk perforation at the 5th week. Subsequently, degenerative arthritic changes were noted. Then, we devised the period of the secondary disk repositioning surgery at the 2nd and 3rd week after experimental disk displacement procedure. Consequently, animals that underwent secondary disk repositioning at the 2nd week showed recovery from hypertrophy and arthritic changes in the cartilage layer. However, secondary operation at the 3rd week showed no recovery, but progressive arthritic changes were noted in the cartilage. Their changes resembled animal condyles without secondary operation. These results indicated a limitation period of the application of disk repositioning procedure for the condition of anterior disk displacement.This project includes another animal experiment relating to mandibular condyle fracture. An artificial rotational dislocation was performed on condyle of adolescent and adult rabbits, then healing process of the fractured fragments were observed. Fractures in the adolescent animals showed complete healing, regardless dislocation angle of the condyle. On the other hand, delayed and incomplete healing of the fractured fragments were noted among adult animals with rotational dislocation of the condyle. These results suggested that open reduction was advocated for condylar fracture in human adults patients. This phenomenon has been continuously investigated with the assessments for enzymatic activities at the fracture site.研究課題/領域番号:10671869, 研究期間(年度):1998-2000出典：研究課題「実験的顎関節症モデルに対する組織学的、生化学的研究」課題番号10671869（KAKEN：科学研究費助成事業データベース（国立情報学研究所）） （https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-10671869/106718692000kenkyu_seika_hokoku_gaiyo/）を加工して作

The change of stress distribution on the condyle after mandibular setback surgery

金沢大学医学部附属病院歯科口腔外科The rigid-body spring model (RBSM) theory was incorporated into a model as a discrete method for analysing problems of limit, such as the stress distribution on the condyle. The purpose of this study was to evaluate the two-dimensional RBSM for determining stress on the temporomandibular joint (TMJ) in patients after orthognathic surgery. Thirty-two patients (five males and 27 females, mean age 21.4 ± 4.9 years) with mandibular prognathism underwent bilateral sagittal split ramus osteotomy (SSRO) and setback; 48 subjects were recruited as controls. Anatomical landmarks were traced from pre- and post-operative lateral cephalograms and the information was processed using the Fortran analysis program. The force vector on the condyle, its degree, its direction, and the displacement co-ordinates (x, y) and rotation (θ) at the gonial angle were calculated. When muscular power was assumed to be 1, the post-operative degree of the force vector was higher than the pre-operative value (P < 0.05). The X co-ordinate, x, and rotation, q, of the displacement vector in the pre-operative patients with mandibular prognathism were significantly higher than those in the control subjects (P < 0.05). There were still significant differences between the displacement values post-operatively between the patients and controls (P < 0.05). The results suggest that the degree and direction of the force vector and the resulting displacement co-ordinates can be used as parameters in a surgical model. The RBSM may also be useful in evaluating the pre- and post-operative skeletal morphology of jaw deformities. © The Author 2006. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved

Comparison of the stress direction on the TMJ in patients with class I, II, and III skeletal relationships.

金沢大学大学院医薬保健研究域医学系OBJECTIVE: To assess the relationship between skeletal morphology and stress direction on the temporomandibular joint (TMJ) by a two-dimensional rigid body spring model (RBSM). DESIGN: Lateral cephalograms were analyzed and the information was processed with a fortran analysis program. SETTING AND SAMPLE POPULATION: The subjects were 149 patients (54 men and 95 women, mean age 21.8 +/- 5.9 years) from Kanazawa University Hospital and the School of Dentistry, Virginia Commonwealth University. Of the 149 cases, 48 were skeletal class I, 54 were class II, and 47 were class III. The patients had no TMJ symptoms or abnormalities. OUTCOME MEASURE: The force vector on the condyle, its direction (Ph angle), the degree of the vector (Ph) and the displacement vector (u, v), and the rotational angle (theta) of the mandibular body were calculated by RBSM. RESULTS: The direction of the force vector (Ph angle) on the condyle was 24.83 degrees +/- 4.67 degrees in the class II group, 21.04 degrees +/- 5.59 degrees in the class I group, and 19.58 +/- 7.57 degrees in the class III group. The Ph angle of the class II group was significantly larger than those of the class I and III groups (p < 0.05). CONCLUSIONS: This study suggests that differences in skeletal patterns induce differences in stress distribution on the TMJ; the morphology of the TMJ was also associated with stress direction and distribution on the condyle

A hypothesis on the desired postoperative position of the condyle in orthognathic surgery: a review

It is very important to clarify the relationship between a dentofacial structure and a temporomandibular joint (TMJ) structure in orthognathic surgery. Recently, it was reported that the skeletal and occlusal patterns were associated with the TMJ morphology, including the disk position. In orthognathic surgery, some surgeons state that alterations in the condylar position from surgery can lead to malocclusion associated with the risk of early relapse, and also favor the development of temporomandibular disorders. For these reasons, several positioning devices have been proposed and applied, but now there is no scientific evidence to support the use of condylar positioning devices. There are some reasons why scientific evidence cannot be obtained; however, it also includes the question of whether the preoperative position of the condyle is the desired postoperative position. The purpose of this study was to verify the desired condylar position in orthognathic surgery, based on literature on the postoperative condylar position in orthognathic surgery. From the studies reviewed, it was suggested that the preoperative position of the condyle was not the desired postoperative position in orthognathic surgery. © 2012 Elsevier Inc. All rights reserved