Growth of a costochondral graft in the rat temporomandibular joint.

The aim of this study was to examine the growth and adaptation of costochondral grafts in the temporomandibular joint (TMJ). An autogenous rib section with either a short, intermediate, or long cartilaginous end was transplanted to replace the right mandibular condyle in 20-day-old rats. At 40 days, the mandibular halves with the short cartilage transplants were shorter than the contralateral halves, whereas the two sides did not differ in length in the rats with the intermediate transplant. The mandibular halves with the longest cartilaginous transplants initially were longer than the contralateral ones. The glenoid fossa was located more laterally as compared with the unoperated side. The results provide evidence that costochondral transplants do not adapt to the functional conditions of the TMJ and that the amount of cartilage in the graft has some bearing on its growth capacity.     

Scaffold and growth factor selection in temporomandibular joint disc engineering

Temporomandibular joint disc tissue-engineering studies commonly fail to produce significant matrix before construct contraction. We hypothesized that poly-L-lactic acid (PLLA) non-woven meshes would limit contraction, allow for comprehensive mechanical evaluation, and maintain viability relative to polyglycolic acid (PGA) non-woven mesh controls. Additionally, we proposed that growth factor stimulation, while limiting contraction, would increase construct properties relative to previous reports. After 4 wks, cell proliferation and matrix deposition were similar between the two meshes, but PGA constructs had contracted significantly. Furthermore, only PLLA constructs could be tested in tension and compression. Additional PLLA constructs were formed, then treated with insulin-like growth factor-1 (10 ng/mL), transforming growth factor-beta 1 (5 ng/mL), or transforming growth factor-beta 3 (5 ng/mL). Transforming growth factor-beta 1 yielded the most cells, collagen, and glycosaminoglycans at 6 wks; these constructs also demonstrated improved mechanics. Analysis of these data demonstrated significant temporomandibular joint disc-engineering potential for PLLA and transforming growth factor-beta 1.     

Expression of vascular endothelial growth factor in human dysfunctional temporomandibular joint discs

A high density of blood vessels is found in specimens of temporomandibular joint (TMJ) disc at any stage of internal derangement of the joint, but the factors responsible for angiogenesis in the disc have not been described. The purpose here was to investigate, in human TMJ discs, the expression of vascular endothelial growth factor (VEGF), a multifunctional cytokine that contributes to angiogenesis. Specimens, free of significant morphological alterations and with varying degrees of disc tissue degeneration/regeneration, were studied by immunohistochemistry for VEGF in order to correlate immunohistochemical with histopathological findings. In normal discs and discs with minor pathological changes, fibroblast-like cells, fibrochondrocytes and chondrocyte-like cells were either not or only weakly immunostained by VEGF antibody. In disc specimens from internal derangement of the TMJ with significant tissue degeneration/regeneration, VEGF was consistently expressed. In these specimens, immunoreaction products for VEGF were observed both in the disc and in the endothelial cells of newly formed vessels. This VEGF immunolocalization is consistent with the stimulation of angiogenesis and the morphogenesis and differentiation of chondrocytes. Therefore VEGF expression by disc chondrocyte-like cells might reflect the action of the cytokine as an inducer of angiogenesis and as an autocrine signal for cells of the chondrogenic lineage.     

Induction of insulin-like growth factor I expression to mandibular advancement in growing rat condylar cartilage]

It was studied effects of functional mandibular advancement on IGF-I peptide of condylar cartilage of 60 5-week-old male rats. Animals were randomly divided into the experimental and control groups, and the mimic functional appliances were used in experimental group. The rats were killed after 1, 3, 7, 14, 21 and 28 days. The results showed that the condylar cartilage of growing rats expressed IGF-I the strongest in the germinal layer, medial in the transitional layer, and the least in the maturational layer. IGF-I positive cells and their immunoreactive levels increased after 1 week of functional mandibular advancement, and reached the peak level at 2 weeks. The results suggest IGF-I in mandibular condyle of rat is related to its growth and differentiation activity, and changes of condylar IGF-I after functional protrusion are relevant to the histologic changes and cellular functions which indicate their involvement with active bone growth and remodeling.     

The role of transforming growth factor-beta, insulin-like growth factor I, and basic fibroblast growth factor in distraction osteogenesis of the mandible.

Distraction osteogenesis is a viable method for regenerating large amounts of bone. In contrast to fracture healing, the mode of bone formation in distraction osteogenesis is primarily intramembranous ossification. The basic biology of the process is still not well understood. The growth factor cascade is likely to play an important role in distraction. This study examines the growth factor cascade in a lengthened ovine mandible model. Twenty-four animals were divided into four groups with varying rates of distraction (1, 2, 3, and 4 mm/day). A unilateral distractor at the angle of the mandible was used. The mandibles were lengthened to 24 mm and fixed for a period of 5 weeks, after which the animals were killed. The sections were probed for transforming growth factor-beta, basic fibroblast growth factor, and insulin-like growth factor I. The growth factors studied were present in all four groups. Transforming growth factor-beta, basic fibroblast growth factor, and insulin-like growth factor I were present in both the bony matrix of the sections and the cytoplasm of the cells, osteoblasts, and a small number of mesenchymal cells. The sections obtained from groups distracted at faster rates showed stronger presence of the growth factors examined by more intense staining. In fracture healing, the localization of transforming growth factor-beta in stage I of healing corresponded with the precise region of intramembranous ossification in stage II. Diffuse presence of transforming growth factor-beta throughout the lengthened region corresponded with the process of intramembranous ossification observed in distraction. In fracture healing, insulin-like growth factor I and basic fibroblast growth factor have been shown to promote proliferation and differentiation of osteoblasts from precursor cells. The intense presence of insulin-like growth factor I and basic fibroblast growth factor in the distracted region may account for osteoblast proliferation and formation from precursor mesenchymal cells. Mechanical strain has been shown to increase the expression of transforming growth factor-beta and insulin-like growth factor I. Distraction may serve as a source of mechanical strain, which may explain, in part, the expression of these growth factors, particularly in the faster groups.     

Platelet-derived growth factor enhances proliferation and matrix synthesis of temporomandibular joint disc-derived cells

Platelet-derived growth factor (PDGF) is an essential signaling molecule for wound healing and tissue repair. This study was aimed at evaluating the effect of PDGF on the proliferation of temporomandibular joint (TMJ) disc-derived cells and extracellular matrix synthesis. The number of cultured cells were counted by COULTER Z1. The assay for collagen synthesis was performed using a sircol soluble collagen assay. Hyaluronic acid (HA) synthesis was analyzed by a high performance liquid chromatography. The expression of collagens, matrix metalloproteinases (MMPs), and the tissue inhibitors of metalloproteinases (TIMPs) were examined using SYBR Green in terms of the RNA levels. PDGF treatment significantly (P < .01) increased the proliferation rate of the disc-derived cells as compared with the controls when the dose was 5 ng/ mL or greater. Treatment with more than 5 ng/mL PDGF resulted in an amount of collagen synthesis significantly (P < .01) higher than the controls. HA synthesis was maximal with 5 ng/mL PDGF treatment. Quantitative real-time polymerase chain reaction analyses showed that treatment with 5 ng/mL of PDGF-BB upregulated the mitochondrial RNA levels of type I and II collagens, MMPs, and TIMPs within 6 hours. It is concluded that PDGF, if its concentration is optimal, enhanced proliferation and matrix synthesis of TMJ disc-derived cells, indicating that PDGF may be effective for use in tissue engineering of the TMJ disc.     

Radiology of the temporomandibular joint. Diagnostic imaging of the temporomandibular joint

Diagnostic imaging plays an important role in the diagnosis of disorders of the masticatory system. The most frequent disorders are osteoarthrosis and internal derangements. The clinical diagnosis of these disorders may be confirmed by diagnostic imaging. In addition, diagnostic imaging contributes to the staging of the degenerative changes. Techniques for examination of the temporomandibular joint, including conventional (panoramic, transpharyngeal, transcranial) as well as more sophisticated techniques (tomography, fluoroscopy, arthrography, computed tomography, scintigraphy and magnetic resonance imaging) are briefly described. The interpretation of the radiological image of the joint in health and when affected by osteoarthrosis and internal derangement is presented.     

Surgical orthodontics and the temporomandibular joint. I. Superior repositioning of the maxilla

Ten randomly selected adults who had undergone orthodontic treatment and isolated superior repositioning of the maxilla for vertical maxillary excess (VME) were evaluated clinically and radiographically (mean, 48.7 months postsurgery) for signs and symptoms of masticatory and temporomandibular joint dysfunction. The patients ranged from 18 years to 37 years of age (mean, 26.2 years) when evaluated. A three-part evaluation of the subjects was performed. This consisted of an anamnestic evaluation (previous medical history), a clinical examination, and a radiographic evaluation. The anamnestic evaluation revealed that, prior to surgery, facial pain was reported by one patient and was not present in any of the patients upon follow-up examination. We believed that the pain was not related to the masticatory musculature and/or the temporomandibular joint. No patients reported pain or sounds in their joints preoperatively, while 30 percent (3/10) of the patients related a history of temporomandibular joint sounds immediately after release of intermaxillary fixation, which subsequently was reported to have resolved in all instances without treatment. Clinical examination of the temporomandibular joints at the time of recall evaluated mandibular movements and the presence of pain or sounds during joint function. These examinations revealed that clinical measures of mandibular movements were somewhat reduced relative to normal. All patients were free of temporomandibular joint and masticatory muscle pain during function, upon contralateral masticatory loading, and upon palpation. Fifteen percent (3/20) of the joints examined demonstrated sounds (popping or crepitation) via auscultation. Masticatory loading in the contralateral premolar region did not induce noise in any of the joints examined. Cephalometric laminagraphic radiographs were obtained of each of the twenty temporomandibular joints with the mandible in three positions; maximum intercuspation, mandibular rest position, and maximal opening. Numerous anatomic relations were quantified from these radiographs. However, only three parameters (condylar position, movement, and evidence of arthrosis) were compared to normative data available in the literature. These comparative data suggested that persons who had undergone orthodontic treatment in conjunction with superior maxillary repositioning demonstrated (1) a relatively retropositional condyle within the fossa and (2) reduced condylar movement during maximal mandibular opening. Two of twenty temporomandibular joints demonstrated radiographic evidence of arthrosis; one condyle demonstrated articular surface erosions, and another exhibited articular surface sclerosis. The overall incidence of arthrosis was not much greater than normal, with 20 percent (4/20) of the joints demonstrating a reduced interarticular joint space. Overall, the clinical findings revealed a low incidence of pathologic masticatory muscle and temporomandibular joint symptoms and signs compared to normative data in the literature...     

Characterization and opioid modulation of inflammatory temporomandibular joint pain in the rat.

PURPOSE: Experimental inflammation of the rat temporomandibular joint (TMJ) is commonly used to study trigeminal nociceptive processing. This study describes spontaneous pain-related behaviors following TMJ inflammation in the rat. The ability of preemptive systemic morphine to attenuate behaviors as well as immediate-early gene expression in the trigeminal nucleus is described. MATERIALS AND METHODS: Adult male Sprague-Dawley rats received an intra-articular injection of mustard oil (0% to 20%, 50 microL) and were observed for behavioral changes. Morphine sulfate (0 to 10 mg/kg SC) was given 30 minutes before mustard oil; this was reversed in one group with naltrexone hydrochloride (5 mg/kg SC). Two hours after injection rats were killed and perfused. Immunohistochemistry for the protein product of the immediate-early gene c-fos was performed, and brain stem sections including the trigeminal subnucleus caudalis were examined for positive nuclei. RESULTS: Mustard oil inflammation of the rat TMJ induces dose-dependent, morphine-sensitive behaviors. Behaviors observed included excessive grooming of the region, a chewing-like behavior, and head shaking. Fos expression in the trigeminal subnucleus caudalis parallels changes in behaviors. Morphine dose dependently attenuates the number of behaviors, as well as Fos expression; this effect is reversed by the micro-opioid receptor antagonist naltrexone. CONCLUSIONS: Mustard oil inflammation of the rat TMJ causes reliable behavioral changes, which may be quantified and, together with Fos expression, used to assess various experimental TMJ treatment modalities.     

The orthopantomogram, an aid in diagnosis of temporomandibular joint problems. I. The factor of vertical magnification

As an orthopantomogram provides bilateral information, it seems to be an efficient tool for screening for arthropathy of craniomandibular disorders. An experimental model was designed and constructed to resemble a human mandible. By changing the position of the model in the horizontal plane of the orthopantomograph, nine different images were analysed for changes of vertical magnifications. Emphasis was put on large parts of the mandible like the condyle. In positions that had been altered less than 10 mm from the originally centred position of the mandible in the orthopantomograph, vertical differences between the left and right sides were less than 6%. Observed condylar asymmetries within a 6% difference might, therefore, be due to technical failures.     

Tumour necrosis factor-alpha and apoptosis in the rat temporomandibular joint

The purpose of this investigation was to investigate the roles that tumour necrosis factor-alpha (TNF-alpha) and apoptosis play during acute inflammation of the temporomandibular joint (TMJ). Adult male Sprague-Dawley rats were injected with complete Freund's adjuvant (CFA) into the TMJ or kept as uninjected controls. The TMJ tissues were removed 2 days post-injection to mimic conditions of acute inflammation and analysed for changes in expression of TNF-alpha, the receptor TNF-R1, caspase-3 and -8, and apoptosis. Concentrations of TNF-alpha, TNF-R1, caspase-3 and -8, and apoptosis were significantly elevated in CFA-injected animals compared to uninjected controls. Tissue incubation with TNF-alpha caused a significant increase in caspase-3 and -8. Also, levels of apoptosis were significantly increased during inflammation, which could be inhibited by the addition of either anti-TNF-alpha neutralising antibody or caspase inhibitors. TNF-alpha may play a significant role in the onset of acute CFA-induced TMJ inflammation, and activation of apoptosis signalling pathways may be involved.     

Immunohistochemical detection of insulin-like growth factors, platelet-derived growth factor, and their receptors in ameloblastic tumors

BACKGROUND: To evaluate the roles of growth factors in oncogenesis and cytodifferentiation of odontogenic tumors, expression of insulin-like growth factors (IGFs), platelet-derived growth factor (PDGF), and their receptors was analyzed in ameloblastic tumors as well as in tooth germs. METHODS: Tissue specimens of 10 tooth germs, 47 ameloblastomas, and five malignant ameloblastic tumors were examined immunohistochemically with the use of antibodies against IGF-I, IGF-II, IGF-I receptor (IGF-IR), PDGF A-chain, PDGF B-chain, PDGF alpha-receptor, and PDGF beta-receptor. RESULTS: Immunohistochemical reactivity for IGFs, PDGF chains, and their receptors was detected predominantly in odontogenic epithelial cells near the basement membrane in tooth germs and in benign and malignant ameloblastic tumors. The expression levels of IGF-II and PDGF chains were significantly higher in ameloblastic tumors than in tooth germs. Malignant ameloblastic tumors showed higher reactivity for PDGF chains than benign ameloblastomas and higher reactivity for platelet-derived growth factor receptors than tooth germs. The expression levels of PDGF chains were significantly higher in follicular ameloblastomas than in plexiform ameloblastomas. Desmoplastic ameloblastomas showed higher expression of IGFs and IGF-IR when compared with other ameloblastoma subtypes. CONCLUSION: Expression of IGFs, PDGF, and their receptors in tooth germs and ameloblastic tumors suggests that these growth factor signals contribute to cell proliferation or survival in both normal and neoplastic odontogenic tissues. Expression of these molecules in odontogenic tissues possibly affects interactions with the bone microenvironment during tooth development and intraosseous progression of ameloblastic tumors. Altered expression of the ligands and receptors in ameloblastic tumors may be involved in oncogenesis, malignant potential, and tumor cell differentiation.     

Postnatal development of the human temporomandibular joint. I. A histological study.

Temporomandibular joints from 61 humans, aged 2 days to 27 years, were examined histologically. Four layers of the condyle were studied in detail. The outermost layer was richly vascularised in new-borns but by 3 years of age it had become avascular and contained few cells. In neonates the cartilage layer constituted a large part of the condyle but soon decreased in thickness and by 5-6 years of age it constituted only a thin zone of the top of the condyle. In the proliferative zone, mitoses occurred up to 13-15 years of age. This zone then decreased in thickness; the number of cells decreased, while the amount of intercellular substance increased. At birth, the temporal component was flat and was lined by vascularised connective tissue which became richer in collagen with increasing age. The cartilage layer was lacking in the fossa but was present on the tuberculum. A proliferative zone in this cartilage could be seen up to the age of 17-18 years and cartilage having only few cells was found in adults. Remodelling processes were seen in all components of the joints. The significance of the remodelling seen in the fossa and on the mandibular neck is discussed with relation to condylar and periosteal growth of the mandible.