Bone morphogenetic protein-2 in temporomandibular joints with internal derangement

OBJECTIVE: The purpose of this study was to analyze the expression of bone morphogenetic protein-2 (BMP-2) in patients with internal derangement of the temporomandibular joint. STUDY DESIGN: Twenty-one human temporomandibular joint samples (5 extirpated disks and 16 biopsy specimens of synovitis area from patients with internal derangement of the TMJ) and 2 control temporomandibular joint specimens (2 normal disks obtained by autopsy) were analyzed with specific antibodies through use of an immunohistochemical technique. RESULTS: BMP-2 was predominantly localized in chondrocytes around the damaged areas of the articular disks. BMP-2 expression was also found in synovial cells and endothelial cells of blood vessels. Control specimens demonstrated BMP-2 staining in synovial lining cells and endothelial cells of blood vessels. However, the chondrocytes in the normal cartilage layers of the control specimens showed no staining. CONCLUSIONS: These findings suggest that BMP-2 may be involved in the pathogenesis of osteoarthritic changes or the repair process of temporomandibular joint internal derangement.     

颞下颌关节骨关节病髁突组织细胞凋亡的研究

目的研究颞下颌关节骨关节病骸突组织中软骨细胞凋亡发生的特点,探讨细胞凋亡在颞下颌关节骨关节病发病机制中的作用。方法通过手术切除部分关节盘的方法建立颞下颌关节骨关节病动物模型,15 d-6个月内采用TUNEL法标记裸突各相应时段的凋亡细胞,结合相应组织学变化,观察、分析颞下颌关节骨关节病裸突组织中细胞凋亡发生的特点。结果关节盘损伤后软骨产生明显应激性修复增殖反应时,凋亡细胞主要集中于关节表面的纤维层中;随着关节软骨和骨组织不断改建,软骨组织中逐渐出现大量的细胞凋亡现象,主要发生于表面纤维层与增殖层,尤其集中在软骨细胞簇中;在软骨组织消耗严重时,浅表区域内的细胞凋亡现象逐渐减少,肥大钙化层中出现了较多的凋亡细胞。结论颞下颌关节骨关节病骸突软骨组织中存在过量凋亡的现象,软骨细胞异常增殖与过度凋亡导致软骨基质自身调节机制的破坏可能是骨关节病发生的重要原因之一。     

MMP-3 and -8 expression is found in the condylar surface of temporomandibular joints with internal derangement

BACKGROUND: Internal derangement is one of the most common disorder of the temporomandibular joint (TMJ). The aim of this study was to investigate the associations of matrix metalloproteinase (MMP)-3 and -8 expression in articular condylar surface with different stages of TMJ internal derangement according to Wilkes (Minn Med, 1978; 61: 645-52) and osteoarthrosis (OA) according to Dijkgraaf et al. (J Oral Maxillofac Surg, 1995; 53: 1182-92). METHODS: The study was based on 54 condylar specimens obtained during TMJ surgery. Immunohistochemistry using antibodies specific to MMP-3 and -8, represented in cartilage destruction, was carried out. RESULTS: In all tissue specimens, MMP-3 expression was intense in the surface layer but showed less intensive staining in the deeper layers. Some MMP-8 expression was also seen. The severity of TMJ internal derangement, however, did not seem to have a statistically significant correlation (P<0.05) with the expression of these enzymes. CONCLUSION: The study confirms that distinct expression of MMP-3 and -8 is found in the condylar surface of TMJs with internal derangement.     

The localization of matrix metalloproteinase-3 and tenascin in synovial membrane of the temporomandibular joint with internal derangement

OBJECTIVES: The aim of this investigation was to study the immunohistochemical localization of MMP-3 and tenascin in the temporomandibular joint and to compare it with control specimens. MATERIALS AND METHODS: Localizations of matrix metalloproteinase-3 (MMP-3) and tenascin in the temporomandibular joint disc and the synovial membrane in 26 human temporomandibular joint samples (internal derangement of TMJ; n = 16, and control; n = 10) by an immunohistological method with monoclonal antibodies specific to human MMP-3 and tenascin. RESULTS: MMP-3 was not distributed in control specimens while it was observed in the internal derangement cases. MMP-3 showed two staining profiles: (1) diffuse staining was observed within the stroma of severely deformed disc with osteophyte and/or disc displacement (three of 16 specimens); and (2) the localization was specifically detected on the surface of severely hypertrophic synovial membrane (six of 16 specimens). The latter localization pattern resembled that of the tenascin on the surface of the severely hypertrophic synovial membrane. CONCLUSION: Comparative localization of MMP-3 and tenascin revealed intense staining for both in the synovial membrane presenting inflammation, proliferation and hypertrophy. These findings suggest that tissue repair and remodeling in the temporomandibular joint disc and the inflammatory hypertrophic reaction in the synovial membrane might proceed at the same time.     

Osteoarthritis and internal derangement of the temporomandibular joint: a light microscopic study

To describe osteoarthritic changes of the temporomandibular joint (TMJ) and their relation to internal derangements, 22 randomly selected TMJ autopsy specimens were dissected and studied by light microscopy. Normal disc position was seen in eight joints, partial anterior displacement of the discs in eight joints, and complete anterior displacement of the discs in five joints; one joint had a perforated disc. Degenerative changes, such as horizontal splitting, clustering of chondrocytes, bone marrow fibrosis, sclerosis, erosion, cyst formation, and reduction in TMJ size, were found in 11 of the 14 joints with displacement or perforation of the disc and in four of the eight joints with normal disc position. Internal derangement appeared to be associated with osteoarthritis. The relations between remodeling, aging, internal derangement, and osteoarthritis are discussed.     

The immunolocalisation of VEGF in the articular cartilage of sheep mandibular condyles.

INTRODUCTION: Vascular endothelial growth factor (VEGF) has recently been found to be essential for hypertrophic chondrocyte apoptosis and angiogenesis at the growth plate of long bones, indicating a central role in endochondral ossification. VEGF has more recently, also been shown to be expressed in articular cartilage chondrocytes in human osteoarthritic and rheumatoarthritic joints but not healthy adult joints. To investigate the role of VEGF in the fibrocartilage of the temporomandibular joint, this study aimed to document the presence and distribution of VEGF in the condylar articular cartilage of sheep temporomandibular joints. METHODS: Mandibular condyles of the temporomandibular joints of five 18-month old Wether sheep were fixed, decalcified, paraffin embedded and sectioned. The sections were analyzed using immunohistochemistry for VEGF. RESULTS: VEGF was found to be localised predominantly to the proliferative and maturing layers of chondrocytes in the condylar fibrocartilage of the temporomandibular joints. Articular cartilage is an avascular and alymphatic tissue. As such, the localisation of VEGF to the articular cartilage of normal temporomandibular joint condyles suggests a role for VEGF other than angiogenesis. CONCLUSION: VEGF is shown here for the first time to be present in mandibular condylar cartilage, leading us to propose a possible role in non-angiogenic extracellular matrix remodeling.     

A histochemical survey of the human temporomandibular joint disc of patients with internal derangement without reduction

This study describes, microscopically, the pathologic findings correlated to malpositioning of the human temporomandibular joint disc. The specimens studied consisted of 21 discs removed from patients affected by temporomandibular joint arthropathy. The specimens were cut longitudinally and were fixed overnight in 10% neutral-buffered formalin. They were embedded in paraffin with anatomic orientation preserved. Three- to 4-microm thick sections were cut according to routine procedures and mounted on slides. Then they were stained with Goldner-modified-Mallory staining used for morphologic study at light microscopy. Abnormal collagen fiber arrangements, fragmentation of collagen fibrils, new vessel formation, meniscal tears, mucoid degeneration of the disc matrix, chondrocyte-like cells proliferation, sometimes with clonal aggregation, and hyalinization were detected in temporomandibular joint disc specimens with internal derangement, although with a different extent. From our observations, it seems that in most cases, the temporomandibular joint disc responded to internal derangement without reduction with a fragmentation of collagen fibers because hyalinization of disc matrix occurred very rarely. Moreover, disc derangement without reduction is characterized also by a change in cell population phenotype.     

Matrix metalloproteinase and its inhibitor in temporomandibular joint osteoarthrosis after indirect trauma in young goats

Our aim was to examine the change in expression of matrix metalloproteinases (MMP-13), matrix metalloproteinases-3 (MMP-3), and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in the articular cartilage of goats with experimentally-induced osteoarthrosis of the temporomandibular joint (TMJ) at various times. Osteoarthrosis was induced in 20 goats in the bilateral TMJ and 5 goats acted as controls. There were 5 goats in each group, and a group was killed at 7 days, and 1, 3, and 6 months postoperatively. The samples were collected, and the joints evaluated histologically. Immunofluorescence was used to detect the presence of MMPs and TIMP-1 in the articular disc and condylar cartilage. The ultrastructure of the articular disc and condylar surface at 1 month was examined with scanning electron microscopy (SEM). Osteoarthrosis of the TMJ progressed gradually over time. MMP-13, MMP-3, and TIMP-1 were expressed strongly in the TMJ soon after injury; MMP-13 became gradually weakened, and MMP-3 strengthened later. None of these were expressed in the normal condyle. After a month the surface of the arthrotic condyle was uneven, and the underlying collagen fibrils were exposed in irregular fissures on the surface. The secretion of TIMP-1 was related closely to the changes of MMPs during osteoarthrosis of the TMJ. The unbalanced ratio between them caused degradation of the matrix of the cartilage and might be the cause of osteoarthrosis of the TMJ.     

Expression of osteoprotegerin in synovial tissue and degradation of articular cartilage: comparison with arthroscopic findings of temporomandibular joint disorders

OBJECTIVE: The aim of this study was to investigate the correlations among the expression of osteoprotegerin (OPG) in synovial tissue and the degree of synovitis, the degeneration of articular cartilage, and the adhesions in patients with internal derangement and osteoarthritis of the temporomandibular joint (TMJ).Study design The expression of OPG, which was detected immunohistochemically, and the degree of arthroscopy of 31 patients with internal derangement and osteoarthritis of the TMJ were assessed and the correlations between them were analyzed statistically. RESULTS: OPG was expressed in the cytoplasm of the endothelial cells, synovial lining cells, and fibroblast cells. TMJs with osteoarthritis had a higher degree of articular cartilage degeneration than did TMJs with internal derangement. There was a correlation between the expression of OPG in the endothelial cells and the degree of the articular cartilage degeneration (P <.01). CONCLUSION: The expression of OPG might be associated with the development of degenerative changes of articular cartilage.     

Microscopic changes in the condyle and disc in response to distraction osteogenesis of the minipig mandible.

PURPOSE: Unilateral mandibular distraction osteogenesis (DO) has been shown to cause gross changes in the mandibular condyle and articular disc. The purpose of this study was to correlate histologic findings with these gross changes in a minipig distraction model. MATERIALS AND METHODS: Semiburied distractors were placed via submandibular incisions in 15 minipigs. Two unoperated animals served as controls. The protocol consisted of 0-day latency and rates of 1, 2, or 4 mm/day for a 12-mm gap. After the minipigs were killed (at 0, 24, or 90 days), ipsilateral and contralateral condyles and discs were harvested, decalcified, prepared for standard paraffin embedding, and evaluated to determine changes in 1) morphology and thickness of the articular cartilage and subchondral bone and 2) morphology of the disc. RESULTS: In control animals, there were no degenerative changes in the articular cartilage and underlying condylar bone; there were no significant differences in the mean articular cartilage thickness. The temporomandibular joint discs were normal. In experimental animals, distracted condyles showed increasing degenerative changes and mean articular cartilage thickness as the DO rate increased. The discs were thinner. These changes were present, but to a lesser degree, in the contralateral condyles. After 90 days, degenerative changes in the condyles and discs were reduced, after remodeling, except in the 4 mm/day DO group. CONCLUSIONS: Histologic changes in the condyles and temporomandibular joint discs in response to mandibular DO correlated with previously reported gross changes. These changes were greater at higher distraction rates and remodeling back to normal occurred in mandibular condyles distracted at 1 mm/day.     

Internal derangement of the temporomandibular joint: a histochemical study.

The purpose of this study was to correlate histologic findings in temporomandibular joint (TMJ) condyles and discs with their macroscopic appearance at surgery. The 24 patients with internal derangement of the joint included 20 women and 4 men (mean age, 37 years; range, 18 to 61 years). The tissue lesions varied in degree from mild soft-tissue fraying and bone remodeling to extensive resorption and new cartilage and bone formation with high phosphatase enzyme activities, and even to loss of articular soft tissue and breakdown of cortical bone. Reactions may arise in the hard tissues before they occur in the articular surface layers.     

自体耳廓软骨瓣置换或重建颞下颌关节盘——临床疗效评价

目的　为了对己严重病变的关节盘进行置换及对关节强直进行重建关节盘 ,本文报道耳廓软骨移植的手术方法和临床疗效 ,并结合文献报道中的有关资料进行讨论。方法　对 4侧结构紊乱、4侧骨关节病、2侧滑膜软骨瘤病及 3侧关节强直 ,共 13侧颞下颌关节 ,用自体耳廓软骨瓣置换或重建关节盘 ,其中 ,6例合并应用关节刨削术 ,2侧用颞深筋膜瓣重建关节外侧囊 ,1侧耳廓软骨瓣复合颞深筋膜修复关节盘以获得足够的厚度。结果　随访期 1～ 13月 ,所有软骨瓣无感染 ,均成活 ,临床疗效满意 ,供区无或轻微变形。结论　在形态和厚度方面 ,人类的耳廓软骨瓣与关节盘较相似 ,是一种置换或重建关节盘的较好材料     

经颧弓后上牵引下颌后关节盘后区适应性改建的实验研究

目的:观察经颧弓后上牵引兔下颌后颞下颌关节盘后区是否发生适应性改建及其意义.方法:在兔下颌角和颧弓处打孔后放置牵引装置,向后上方牵引下颌,于术后2、4、6 周分别处死动物,采用组织学及免疫组化方法观察负荷下关节盘后区组织的改变.结果:术后2 周兔牵引侧关节盘移位或变形,盘后区胶原密度增加;随着负荷时间的延长,关节后区成纤维细胞密度明显下降,关节盘后区结缔组织变得致密,组织内出现少量软骨样细胞出现,而对照组标本未见明显组织学改变.与对照组相比,术后2 周移位的关节盘功能区软骨基质、蛋白聚糖及Ⅱ型胶原呈弱表达,阿辛蓝染色变淡;移位至负重区的关节盘后区软骨基质、蛋白聚糖表达比对照组有所增加.随着关节负荷时间的延长,移位至负重区的关节盘后区软骨基质、蛋白聚糖及Ⅱ型胶原逐渐增强.结论:经颧弓后上牵引下颌后,关节盘后区组织内软骨基质合成增加,并有少量软骨细胞出现,发生改建以适应关节功能.     

Immunolocalization of gelatinase-A (matrix metalloproteinase-2) in damaged human temporomandibular joint discs.

The fibrous tissue of the articular disc of the dysfunctional temporomandibular joint undergoes deep and variable structural modifications. Here the concurrence of morphological changes and the expression of matrix metalloproteinase-2 (MMP-2) in damaged discs from individuals suffering joint dysfunction was investigated. Microscopic, ultrastructural and immunocytochemical investigations were made on variously damaged articular discs and on one control sample. Disaggregation of collagen fibres, an increase in cellular components and calcification of large areas of tissue were observed in the damaged discs. These modifications were accompanied by a positive immunoreaction pattern for MMP-2. Fibroblast-, chondroblast- and osteoblast-like cells displayed a positive cytoplasmic reaction. In samples displaying evidence of synovial hyperplasia, some cells of the synovial protrusions were MMP-2 immunoreactive. No MMP-2 staining was observed in the control sample. These findings demonstrate that structural modifications of the articular disc could be specific responses to changes in the function of the temporomandibular joint. Variations in extrinsic stimuli may activate intrinsic factors, such as MMPs, that induce structural modifications in the discal tissue.     

医用臭氧对颞下颌关节骨关节炎大鼠髁突软骨作用研究

目的    分析于颞下颌关节腔内注射医用臭氧对颞下颌关节骨关节炎（temporomandibular joint osteoarthritis，TMJOA）大鼠髁突软骨的作用。方法    选取8 ~ 10周龄雄性SD大鼠22只，随机分为对照组6只、模型组6只、实验组10只。模型组和实验组大鼠建立TMJOA模型3周后，实验组大鼠颞下颌关节腔内注射质量浓度为30 μg/mL的医用臭氧，其他2组注射生理盐水，每周1次，共3次。行锥形束CT（cone beam computed tomography，CBCT）扫描后处死各组大鼠并进行取材，观察髁突和关节盘的变化；采用HE、甲苯胺蓝染色并分别通过改良Mankin′s评分和平均光密度值分析髁突软骨细胞和基质的变化情况；采用抗酒石酸酸性磷酸酶（tartrate-resistant acid phosphatase，TRAP）染色观察破骨细胞数量及分布。结果    经CBCT检查和肉眼观察发现，模型组和实验组颞下颌关节髁突及关节盘呈现出不同程度的缺损，模型组缺损程度重于实验组。3组改良Mankin′s评分、平均光密度值和TRAP染色阳性细胞数比较，差异均有统计学意义（F值分别为93.462、44.498、113.918，均P < 0.05）。其中，模型组和实验组的改良Mankin′s评分、TRAP染色阳性细胞数均大于对照组，模型组这2个指标还高于实验组，差异均有统计学意义（均P < 0.05）；模型组和实验组的平均光密度值低于对照组，模型组的平均光密度值低于实验组，差异均有统计学意义（均P < 0.05）。结论    于颞下颌关节腔内注射质量浓度为30 μg/mL的医用臭氧，可减轻TMJOA大鼠髁突软骨及软骨下骨的损伤。     

颞下颌关节紊乱病动物模型的建立及其评价

目的探讨经颧弓后上牵引下颌，建立颞下颌关节紊乱病（TMD）动物模型的可能性。方法21只新西兰大白兔（实验组15只，对照组6只），单侧经颧弓后上牵引下颌，观察关节盘、关节间隙及关节软骨的组织病理学改变。结果实验组术后2周4只动物关节盘移位或变形；4周时5只动物关节均发生粘连，关节软骨发生不同程度表层破裂、缺损或排列紊乱；6周时4只动物关节盘严重变形，5只动物关节发生严重粘连，骨小梁排列紊乱。对照组均正常。结论经颧弓后上牵引下颌是研究TMD病理机制一种较可靠的动物模型。     

Analysis of 70Kd heat shock protein expression in patients with internal derangement of the temporomandibular joint

Recent studies have demonstrated that the expression of heat shock protein (HSP) was enhanced under stress in joint diseases, such as rheumatoid arthritis and osteoarthritis. The purpose of this study was to analyze the expression of 70Kd HSP in patients with internal derangement of the temporomandibular joint (TMJ) by immunohistochemical and enzyme-linked immunosorbent assay (ELISA) methods. For immunohistochemistry, 5 extirpated discs and 16 synovial biopsy specimens from patients with TMJ internal derangement and 2 extirpated discs from normal subjects were examined. For ELISA, synovial fluid from 11 patients with TMJ internal derangement and from 6 normal volunteers were investigated. The results showed that the 70Kd HSP staining intensity in chondrocytes around the damaged area of the articular discs from patients with TMJ internal derangement was higher than that in chondrocytes in control specimens. In addition, 70Kd HSP expression in synovial fluid from patients with TMJ internal derangement was slightly higher than that in normal subjects. These findings suggest that elevated 70Kd HSP expression is related to the progression of TMJ internal derangement.     

颞下颌关节间接性损伤后MRI表现及其意义

目的：研究羊颞下颌关节（TMJ）间接性损伤后关节结构的变化。方法：用自制撞击装置造成山羊双侧颞颌关节间接性损伤,分别于伤后2h、7h、1月、3月行MRI观察后处死取材,并进行组织学观察,正常关节作为对照,结果：TMJ损伤后MRI观察发现：TMJ间接性损伤后可导致关节软、硬组织结构的变化。在损伤早期1月内表现为髁突表面软骨的碎裂,关节盘挫裂和移位,关节间隙的减小和关节腔内出现血性渗液;在损伤后期1-3月表现为髁突表面软骨的破坏和吸收,关节盘畸形,关节间隙减小,结论：MRI不但能够清楚、全面地反映关节损伤后软、硬组织结构和形态的变化,还是一种可用于研究TMJ损伤后转归和后遗症发生机理的较好的、精确的观察手段。     

Diagnostic accuracy of fat-saturated T2-weighted magnetic resonance imaging in the diagnosis of perforation of the articular disc of the temporomandibular joint

The accuracy of diagnosing a perforation of the articular disc of the temporomandibular joint (TMJ) is poor with conventional magnetic resonance imaging (MRI). We recently reported that a high signal-intensity area is usually found on fat-saturated T2-weighted MRI in the joint space between the articular disc and cartilage surface in joints in which the disc is displaced. A discrete image with an area of high signal-intensity in the middle of the articular disc may indicate perforation or rupture. The purpose of this study was to compare the accuracy of diagnosis of a perforated articular disc by fat-saturated T2-weighted MRI with that of arthroscopy. We studied 50 joints in 50 patients with closed lock of the TMJ who were examined with MRI and then by arthroscopy using an ultra-thin arthroscope. The agreement between the two methods of diagnosis was assessed using the κ coefficient. Evidence of perforation of the disc on MRI and arthroscopically was found in the same 7 joints; there was complete concordance (κ=1.00, p<0.001). The accuracy of diagnosis of perforation of a disc by fat-saturated MRI was therefore the same as that by arthroscopy using an ultra-thin arthroscope.     

The expression of cyclooxygenase-2 in human temporomandibular joint samples: an immunohistochemical study

The aim of this investigation was to evaluate the immunohistochemical expression of cyclooxygenase-2 (COX-2) in the temporomandibular joint (TMJ) and to compare it with that control specimens. Expression of COX-2 in the TMJ disc and the synovial membrane in 26 human TMJ samples (internal derangement of TMJ; n=16, and control; n=10) was measured by an immunohistological technique using paraffin-embedded tissue and specific antihuman COX-2 polyclonal antibody. There were obvious distinction of COX-2 immunoreactivity between the control specimens and internal derangement cases, in the region of posterior and/or anterior loose connective tissues. In particular, intensive COX-2 expression was detected in the synovial membrane of internal derangement cases. The findings of the present study suggest that COX-2 might be an important mechanism regulating inflammation in the synovial membrane with internal derangement of TMJ.