关节腔内早期注射阿仑膦酸钠对卵巢摘除大鼠髁突软骨下骨的影响

目的：研究卵巢摘除的雌性大鼠,关节腔内早期注射阿仑膦酸钠对髁突软骨下骨的影响。方法将60只雌性SD大鼠随机分成5组：卵巢切除后使用空白载体治疗组、术后早期注射阿仑膦酸钠治疗组、术后4周（晚期）注射组、假手术后使用空白载体治疗组和正常对照组。利用Micro?CT、抗酒石酸酸性磷酸酶（tar?trate resistant acid phosphatase ,TRAP）染色以及实时定量聚合酶链反应（qRT?PCR）来检测髁突软骨下骨的变化。结果早期注射阿仑膦酸钠可以明显改善软骨下骨的微观结构,与晚期注射组相比,主要表现在其具有更高的骨体积比（46.4±2.5 vs 37.5±2.1;P=0.038）、骨小梁厚度（47.3±1.7 vs 34.6±1.4;P=0.029）、骨小梁数目（8.5±0.6 vs 6.2±0.3;P=0.041）及更少的骨小梁分离（30.2±1.6 vs 37.7±2.6;P=0.034）。与其他3组比较,早期注射组大鼠软骨下骨中的TRAP阳性细胞更少（4.2±0.2 vs 6.8±0.4;P=0.019）以及OPG/RANKL比例更高（0.38±0.01 vs 0.25±0.03;P=0.043）。结论关节腔内早期注射阿仑膦酸钠可以有效改变软骨下骨的微观结构,减轻髁突软骨的病变程度。     

颞下颌关节软骨下骨改建

颞下颌关节改建机制是正畸功能矫形和颞下颌关节紊乱病研究的主要内容。随着研究的深入,软骨下骨作为一个生物力学和生理学特性均有别于关节软骨和骨松质的基本功能单位,其在压力传递和关节改建中的重要性逐步凸现出来。本文就软骨下骨的解剖、功能、特性、病变类型以及与颞下颌关节改建的关系作一综述。     

Installing and thereafter removing an aberrant prosthesis elicited opposite remodelling responses in growing mouse temporomandibular joints

Temporomandibular joint (TMJ) displays a high remodelling capability. The current purpose was to investigate the differences between mandibular condylar remodelling responses of growing mice to installation and removal of unilateral anterior crossbite (UAC) prosthesis. Twenty‐four mice were divided into one mock control group and two UAC groups. Unilateral anterior crossbite was created by installing a pair of prosthesis to left‐side maxillary and mandibular incisors. Unilateral anterior crossbite was removed in removal group at 3 weeks but remained in UAC group. Temporomandibular joints were sampled at 7 weeks. Changes in condylar cartilage and subchondral bone were assessed by histology and in vivo micro‐CT. Real‐time PCR and immunohistochemistry were performed to evaluate expression changes in ADAMTS‐5, MMP‐3, MMP‐9, MMP‐13, IL‐1, TNF‐α, OPG and RANKL. Statistical analysis was performed at α = 0·05. Temporomandibular joint cartilage degradation was induced by UAC as previously reported but was reversed by removal of UAC. The dropped cartilage thickness, chondrocyte number and collagen II‐positive area, the increased expression levels of Adamts‐5, Mmp3, 9, 13, Tnf‐α and Il‐1β in cartilage, the decreased ratio of OPG/RANKL in both condylar cartilage and subchondral bone, the loss of TMJ subchondral bone and the increase in the TRAP‐positive cells in subchondral bone were all reversed in the removal group (P < 0·05). The growing mouse TMJ condyle displays a high remodelling capability which can be degenerative and rehabilitative, respectively, in response to placement and thereafter removal of the aberrant prosthesis. Eliminating aberrant prosthesis is helpful to promote the degraded condyle to recover.     

Decreased bone marrow stromal cells activity involves in unilateral anterior crossbite-induced early subchondral bone loss of temporomandibular joints

Objective

Subchondral bone loss in mandibular condyles was reported to be induced by experimentally created unilateral anterior crossbite (UAC) which altered the occlusal load distribution and hereafter the temporomandibular joint (TMJ) remodelling process. However, the initial cellular responses are poorly understood. In the present study, changes in osteoblast and osteoclast activities in TMJ subchondral bone were investigated using the rats treated with UAC.

Design

Forty rats were randomly divided into UAC and control groups, and sampled at 2 weeks after the operation. Subchondral bone loss was evaluated by micro-CT. Osteoclast and osteoblast activities were analyzed by real-time PCR. The osteoblast differentiation of the locally isolated BMSCs from TMJ subchondral bone was assessed by Alizarin red staining. The migration of BMSCs was detected by transwell assays.

Results

Compared with the age-matched controls, TMJ subchondral bone loss was observed in the UAC-treated rats (p < 0.05). The osteoblast activity evaluated by real-time PCR and osteoblast number revealed by immunohistochemical staining were reduced in the TMJ subchondral bone of UAC rats (p < 0.05), and the capability of proliferation, migration and osteoblast differentiation were all decreased in the locally isolated BMSCs from the UAC group (p < 0.05).

Conclusions

The present data demonstrated an involvement of reduced BMSCs activity in the initiation of the mandibular subchondral bone loss at the early stage of installation of the aberrant prostheses.     

Dynamic changes in bone metabolism in the rat temporomandibular joint after molar extraction using bone scintigraphy

Functional adaptation with reformation of bone tissue structure occurs after changes in mechanical stress distribution. To examine how occlusal changes affect the dynamics of bone metabolism in the mandibular condyle, bone scintigraphy of rat condyles was taken using ^99mtechnetium-methylene-diphosphonate (^99mTc-MDP) after extraction of maxillary molars resulting in unilateral loss of occlusal support. Accumulation of ^99mTc-MDP was significantly higher in the condyles on the extracted side than on the intact side 3 d after molar extraction. In addition, bone mineral density (BMD) and osteoprotegerin expression in extracted-side condyles were significantly increased while osteoclast numbers were significantly decreased when compared with intact-side condyles. These differences were not detected 28 d after molar extraction. These findings suggest that occlusal change transiently results in changes in the dynamics of bone metabolism at the mandibular condyles through the downregulation of osteoclastogenesis. These changes may be involved in functional adaptation of the temporomandibular joint.     

Insulin-like growth factor-1 suspended in hyaluronan improves cartilage and subchondral cancellous bone repair in osteoarthritis of temporomandibular joint

This study sought to evaluate the effects of intra-articular injection of insulin-like growth factor-1 (IGF-1) suspended in hyaluronan (HA) on the cartilage and subchondral cancellous bone repair in osteoarthritis (OA) of the temporomandibular joint (TMJ). Disc perforation was performed bilaterally in rabbit TMJs to induce OA. Four groups of animals (n = 12) received OA induction only, and either intra-articular HA injection alone, intra-articular IGF-1 injection alone, or a combination of HA and IGF-1 injection. All therapy was begun 4 weeks after OA induction. The animals were killed 12 or 24 weeks after the first injection, for histology and micro-CT examinations. Two additional animals were used as normal controls. Typical cartilage and subchondral cancellous bone lesions were observed in the OA group. No protective effect on cartilage and subchondral cancellous bone was found in the HA or IGF-1 alone groups. Better histological repair and nearly normal micro-architectural properties of the subchondral cancellous bone were observed in the HA + IGF-1 group compared with the HA or IGF-1 alone groups. HA may be used as an effective carrier for intra-articular injection of IGF-1 and the combination of HA/IGF-1 shows promise as a new rational approach to therapy of TMJ OA.     

Severe temporomandibular dysfunction and joint destruction after intra-articular injection of triamcinolone

BACKGROUND: Steroid injections into joints are frequently used to control symptomatic pain. Risks associated with intra-articular steroid injections are not well documented. METHODS: We report the case of a 29-year-old woman who was referred to a dental surgeon because of a suspected relationship between persisting chronic back pain and an arthrosis of the temporomandibular joint (TMJ). RESULTS: The dental surgeon diagnosed capsulitis of the right TMJ and injected 40 mg triamcinolone into the joint. Within 4 months the patient developed progressive pain and trismus of the right TMJ and the intra-articular injection was repeated. An occlusal splint slightly improved the patients' symptoms but induced crepitus. Magnetic resonance imaging revealed a disk dislocation in the right TMJ and severe necrosis of the condyle. The patient had persisting pain and ankylosis. Surgical restoration of the TMJ revealed a bony apposition in the fossa deformed with the socket of the joint, extensive medial erosion of the condyle and complete destruction of the disk. CONCLUSION: This case report supports earlier observations that intra-articular glucocorticoid injections, if used in a wrong way, may cause severe destruction of a joint.     

Quantitative histological changes of repeated antigen-induced arthritis in the temporomandibular joints of rabbits treated with intra-articular corticosteroid

Background:  To compare the inflammatory changes of antigen-induced temporomandibular joint (TMJ) arthritis in rabbits by different histological methods and to evaluate the immunomodulatory effect of intra-articular corticosteroid injections histologically.
Methods:  35 rabbits (10 weeks old) pre-sensibilized with ovalbumin were divided into three groups: a placebo group of five (saline), an arthritis group of 15 (ovalbumin) and a steroid-treated group of 15 (ovalbumin + corticosteroid). Additionally, a group of seven rabbits receiving no sensibilization with ovalbumin and no intra-articular injections served as controls. Histomorphometry of the inflammatory changes in the subsynovial connective tissue (SSCT) of the TMJ included: (i) semi-quantitative (S-Q) scoring of inflammation and synovial proliferation, (ii) thickness measurements and fractional surface and (iii) stereological quantitative assessment of volume and plasma cells in thick sections of the SSCT by an optical fractionator.
Results:  The histomorphometry showed synovial proliferation in both the arthritis and the steroid groups. The plasma cell count obtained by the optical fractionator was significantly reduced when treating the TMJ with corticosteroids. However, the thickness of the synovial lining and volume of the SSCT as well as S-Q scoring of inflammation showed no difference between the arthritis and the steroid-treated groups. The optical fractionator proved a superior tool compared to S-Q assessments.
Conclusion:  Counting of plasma cells in the SSCT showed that corticosteroids reduced the inflammation, but did not eliminate it. Semiquantitative scoring of synovial proliferation and inflammation demonstrated low sensitivity regarding changes in immunomodulation in antigen-induced arthritis compared to stereological quantitative estimations using an optical fractionator.     

Applying an excessive mechanical stress alters the effect of subchondral osteoblasts on chondrocytes in a co‐culture system

Lin Y‐Y, Tanaka N, Ohkuma S, Iwabuchi Y, Tanne Y, Kamiya T, Kunimatsu R, Huang Y‐C, Yoshioka M, Mitsuyoshi T, Tanimoto K, Tanaka E, Tanne K. Applying an excessive mechanical stress alters the effect of subchondral osteoblasts on chondrocytes in a co‐culture system. Eur J Oral Sci 2010; 118: 151–158. © 2010 The Authors. Journal compilation © 2010 Eur J Oral Sci Osteoarthritis (OA) sometimes occurs as a consequence of repeated microtrauma involved in parafunction, which may lead to microfracture in the subchondral bone. The aim of this in vitro study was to evaluate the effects of subchondral osteoblasts in loading with repeated excessive mechanical stress on the metabolism of overlying chondrocytes. A high‐magnitude cyclic tensile stress of 15 kPa (30 cycles min^?1) was applied to the cultured osteoblasts obtained from porcine mandibular condyles. The chondrocytes in alginate beads were then co‐cultured with mechanically stressed or unstressed osteoblasts. Chondrocytes co‐cultured with unstressed osteoblasts showed a phenotypic shift to hypertrophic chondrocytes, characterized by decreased expression of type II collagen, aggrecan, Sry‐related HMG box (SOX‐9), and cartilage oligomeric matrix protein (COMP) genes and increased expression of type X collagen and bone sialoprotein (BSP) genes, suggesting that the co‐culture may change the chondrocyte differentiation to some extent. These changes were more distinct in chondrocytes co‐cultured with excessively mechanically stressed osteoblasts. After co‐culture with stressed osteoblasts, the expressions of matrix metalloproteinase (MMP)1, MMP3 and MMP13 genes were also enhanced and the synthesis of DNA, proteoglycan and collagen were significantly decreased in chondrocytes. These results demonstrate that alterations in cartilage metabolism can be induced by stressed osteoblasts, indicating a possible explanation for the onset and progression of OA.     

大鼠双侧卵巢切除后颞下颌关节的组织学研究

目的 观察成年大鼠双侧卵巢切除对颞下颌关节（ｔｅｍｐｏｒｏｍａｎｄｉｂｕｌａｒ ｊｏｉｎｔ，ＴＭＪ）组织学的影响。方法 ６８只２０周龄雌性ＳＤ大鼠分为２组，用切除是卵巢作为实验组，假手术组作为对照组。分别在术后１、２、４、８和１２周处死动物，用光镜、扫描电镜和透射电镜观察大鼠ＴＭＪ组织学变化，同时检测血清雌二醇（Ｅ２）和股骨骨密度。结果 各程期实验组血Ｅ２均明显低于对照组。１２周时，实验检测血清雌     

Morphometric investigation of condylar cartilage and disc thickness in the human temporomandibular joint: significance for the definition of ostearthrotic changes

106 human TMJ specimens from 53 individuals (age: 65–85 years) were examined macro- and microscopically and measured for discal and condylar cartilage thickness at five points defined on a mediolateral axis along the middle dense pan of the disc. 27% of the discs showed lateral and laterocentral perforations. In 8% the lateral portion was thinned down to a translucent layer. 62% showed no gross destruction or deviation in shape and thickness. The remaining 3% displayed extensive destruction and their condyles were osteoarthrotic. All discs showed a significant decrease in thickness from their medial towards their lateral portions. The condyles displayed either a smooth articular surface (16%) or an irregular and progressively remodelled surface (81%) with histologically normal fibrocartilage. The condylar cartilage did not show a significant gradient of thickness in amediolateral direction. The results support our previously developed working hypothesis, that the joint is seemingly loaded along its entire articular surface and that a lateral disc perforation in older individuals can be due to a physiological process of wearing rather than to a pathological sequel of functional disorders.     

Cartilage matrix macromolecules in lavage fluid of temporomandibular joints before and 6 months after diskectomy

The purpose was to investigate if antigenic fragments of aggrecan and cartilage oligomeric matrix protein (COMP) are detectable by enzyme-linked immunosorbent assay in lavage fluids from the temporomandibular joint (TMJ) and to examine if the relative content of these cartilage markers changes during development of osteoarthrosis (OA) after diskectomy. Lavage fluid was obtained at surgery and 6 months postoperatively in 13 patients. Computed tomography or magnetic resonance imaging was without evidence of hard-tissue changes prior to surgery in all patients. In 9 of the patients, sufficient material for analysis was obtained at both examinations. Aggrecan and COMP were detectable in all but 2 fluids, in which the COMP levels were below detection limit. The aggrecan/COMP ratio increased in all 9 patients during the 6-month period, indicating increased release of aggrecan relative to COMP fragments. The changed aggrecan, COMP ratio possibly reflects increased cartilage turnover during development of OA. Changes compatible with OA were present on computed tomography in all cases at the 6-month follow-up. This study shows that the lavage procedure is feasible for obtaining synovial fluid from the TMJ for immunochemical analyses of tissue-derived macromolecules.     

Alteration of BMP-4 and Runx2 expression patterns in mouse temporomandibular joint after ovariectomy

OBJECTIVE: Temporomandibular disorder (TMD) includes a number of clinical conditions involving the masticatory musculature or the temporomandibular joint (TMJ) and associated structures. Previous studies have shown the presence of high-affinity estrogen receptors in the TMJ articular cartilage. The aim of this study was to evaluate the developmental changes in mouse TMJ under estrogen deficiency. MATERIALS AND METHODS: Four-month-old ovariectomized mice were killed after certain weeks. We examined the significant alterations of the expression patterns of bone morphogenetic protein (BMP)-4, Runx2, and bone sialoprotein (BSP) after ovariectomy. Results: In the control group, BMP-4, Runx2, and BSP expressions showed no definite difference at any stage. In the ovariectomy group, the intensity of BMP-4 and Runx2 expression increased after ovariectomy. BSP immunoreactivity, however, increased slightly at 2 weeks but then decreased gradually. CONCLUSIONS: Estrogen plays important roles in the metabolism and maintenance of TMJ via regulations of signaling molecules such as BMP-4, Runx2, and BSP. Our results suggest that estrogen deficiency is a candidate cause of TMD. This study revealed further osteogenetic properties of estrogen that may be useful in the clinical treatment and prevention of TMD.     

可复性关节盘前移位对颞下颌关节三维形态学参数的影响

目的通过三维形态学测量方法探究可复性关节盘前移患者(ADDwR)与正常人颞下颌关节(TMJ的差异。方法招募了15名ADDwR患者和10名无症状的正常人,在MIMICS 20.0软件中重建出上、下颌骨的三维模型,在三维模型上测量双侧TMJ的9个形态学参数,分析ADDwR患者患病侧与正常人两侧之间的差异。结果 ADDwR患者患侧的水平髁突角、冠状髁突角均显著大于正常人(P<0.01),矢状升支角、关节腔内间隙、关节腔外间隙、关节腔上间隙、关节腔前间隙和关节腔后间隙均显著小于正常人(P<0.01)。结论ADDwR将导致患病侧的髁突角显著大于正常人,下颌矢状升支角、关节间隙显著小于正常人,从而导致髁突向上移位,更接近关节窝。     

Chondrotoxic effects of intra-articular injection of local anaesthetics in the rabbit temporomandibular joint

The aim of this study was to investigate the chondrotoxic effects of a single-dose intra-articular injection of articaine, lidocaine, and bupivacaine on the rabbit temporomandibular joint (TMJ). Twenty-four rabbits were divided into four groups: control (group 1), articaine (group 2), lidocaine (group 3), and bupivacaine (group 4). Synovial fluid samples and venous blood were taken to evaluate matrix metalloproteinase 3 (MMP-3) levels. One millilitre of local anaesthetic solution was injected in the study groups and saline solution in the control group. The rabbits were euthanized after 4 weeks and the mandibular condyles and articular discs were evaluated. On histological examination, the study group samples had irregular joint surfaces, decreased collagen, and a thinner cartilage layer. Apoptotic cells were evaluated with the TUNEL method. TUNEL-positive apoptotic cell counts were higher in all study groups compared to the control group, and the difference was significant (P < 0.001). The mean preoperative serum MMP-3 level for all groups was 5.71 ± 3.33 ng/mL, while the mean postoperative level was 22.61 ± 6.36 ng/mL; this difference was significant (P < 0.001). A single-dose intra-articular injection of local anaesthetic had apoptotic effects on chondrocytes, leading to degenerative changes in the TMJ articular structures. Articaine was found to have less harmful effects than lidocaine and bupivacaine. Intra-articular injection of local anaesthetics should be limited in the TMJ because of the potential toxic effects.     

咬合重建前后颞下颌关节症状及骨性结构影像学改变的研究

目的研究咬合重建前后颞下颌关节症状及骨性结构的影像学变化。方法选择2011年1月至12月口腔修复门诊需咬合重建的患者20例,分别在修复前及修复后3个月进行颞下颌关节临床症状及锥形束CT影像学检查,在垂直于髁状突横轴的矢状位重建影像,测得关节前、中、后间隙。结果进行卡方检验、配对样本均数t检验以及直线相关分析。结果经过3个月的咬合重建修复,患者咀嚼肌和关节区压痛有显著改善,关节弹响未见明显好转。CBCT结果显示咬合重建后关节前间隙减小、后间隙增大,直线相关和回归分析显示关节后间隙的改变与咬合增高距离相关,并推导出线性回归方程。结论测量关节后间隙对确定咬合增高的距离有一定的参考价值。     

情绪应激对大鼠咀嚼肌肌电图及颞下颌关节微结构的影响

目的:观察情绪因素对咀嚼肌肌电图和颞下颌关节(temporomandibular joint,TMJ)的影响,探讨情绪应激在颞下颌关节病发病中的作用。方法:90只SD大鼠,随机分为对照组,心理应激组和足部电击组,人为造成情绪刺激的动物模型。分别在0天,1周,3周和5周后进行肌电图检查,并通过扫描点镜观察TMJ的结构变化。结果:无论是实验1周、3周和5周其松弛状态或紧咬时颞肌、咬肌的电位明显高于0天,且两侧无明显差别,同时,情绪刺激组双侧颞肌和咬肌的肌电图静息期较对照组显著延长;情绪应激1周时,大鼠髁突软骨表面的凝胶样物开始出现不完整,剩余的堆积呈纤维条索样,且可见到髁突表面胶原纤维暴露且排列紊乱。3、5周组大鼠髁突表面有宽窄不等、深浅不一的微小裂隙。结论:情绪应激可以对咀嚼肌肌电图和TMJ的结构造成影响,可能是颞下颌关节紊乱病的病因之一。