Qinggong Meng

Role of NF-κB in TNF-α-induced COX-2 Expression in Synovial Fibroblasts from Human TMJ

In the temporomandibular joint (TMJ) synovium, cyclo-oxygenase-2 (COX-2) expression has been believed to be directly related to joint pain and synovitis. Here we investigated the role of Nuclear Factor κB (NF-κB) in the regulation of COX-2 expression in synovial fibroblasts from human TMJ induced by tumor necrosis factor-α (TNF-α). By reverse-transcriptase/polymerase chain-reaction (RT-PCR) and Western blotting analysis, TNF-α induced a dose- and time-dependent increase in COX-2 expression. Electrophoretic mobility shift assay (EMSA) revealed that transient NF-κB activation in the COX-2 promoter was triggered by TNF-α. In parallel with transient NF-κB activation, the rapid translocation of NF-κB, particularly the p65 subunit, from the cytoplasm into the nucleus was demonstrated. Pre-treatment with pyrolidine dithiocarbamate (PDTC), one of the NF-κB inhibitors, prevented binding to the COX-2 promoter and expression of COX-2 protein in response to TNF-α. These findings indicate that activation of NF-κB is responsible for TNF-α-induced COX-2 expression in synovial fibroblasts from the TMJ.

A randomized controlled trial of superior and inferior temporomandibular joint space injection with hyaluronic acid in treatment of anterior disc displacement without reduction

PURPOSE To compare the outcome of inferior and superior joint space injection of sodium hyaluronate in patients with disc displacement without reduction of the temporomandibular joint (TMJ). MATERIALS AND METHODS One hundred twenty patients with disc displacement without reduction of TMJ were randomized into 2 experimental groups. One group of patients received superior joint space injections of sodium hyaluronate and the other group was treated with inferior joint space injections. Patients TMJ status and clinical symptoms were evaluated at the 3 and 6 month follow-up appointments. The clinical parameters recorded were maximal mouth opening (MMO), pain intensity on a visual analog scale (VAS), and modified Helkimos clinical dysfunction index and analyzed with ANCOVA. RESULTS Fifty of the superior and 54 of the inferior joint space injection therapy group returned for the 3 and 6 month evaluations; 86.67% of the patients were retained in the follow-up. MMO, VAS, and Helkimos index of both groups improved at the 3 and 6 month follow-ups. The results of MMO changes and TMJ function were almost the same in both groups at 3 month follow-up. However, there was a significant reduction in TMJ pain in the inferior joint injection group at 3 month follow-up compared with the superior joint injection group (P< .001). There were also significant differences between the inferior joint injection group and superior joint injection group in MMO (P< .005), VAS (P< .001), and Helkimos index (P< .001) at 6 month follow-up. CONCLUSION This study showed that inferior joint space injection with sodium hyaluronate is a valid method of treating disc displacement without reduction of TMJ and a long-term study will be needed to assess the effect of inferior joint injection on the morphologic changes of the TMJ.

Insulin-like growth factor-1 boosts the developing process of condylar hyperplasia by stimulating chondrocytes proliferation.

OBJECTIVE The etiology of Condylar hyperplasia (CH) of human temporomandibular joint (TMJ) remains largely unknown. Our previous study has demonstrated that enriched insulin-like growth factor-1(IGF-1) was expressed in the proliferation and hypertrophic layers of CH cartilage. Accordingly, this study was aimed to investigate whether IGF-1 regulates CH chondrocytes proliferation in condylar cartilage overgrowth and explore the molecular mechanism of IGF-1 involved in. METHODS Chondrocytes were isolated from 6 CH and 3 normal cartilage (NC) specimens and cultured in alginate beads or monolayer, treated with IGF-1 or specific inhibitors such as 7-[trans-3-[(azetidin-1-yl)methyl]cyclobutyl]-5-(3-benzyloxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (NVP-AEW541), U0126, and LY294002. Thereafter, cellular proliferation capacity was evaluated by Cell Viability Analyzer (alginate beads culture) or 3-(4,5-dimethylthiazo(-2-yl)-2,5-diphenyltetrazolium bromide (MTT) (monolayer culture). Gene expression levels of IGF-1, IGF-1 receptor (IGF-1R), collagen type II, type X and those genes associated with proliferation were evaluated by realtime PCR. Protein levels of IGF-1 and IGF-1R synthesized by CH chondrocytes were accessed by enzyme-linked immunosorbent assay (ELISA) and western blotting. RESULTS CH chondrocytes enhanced cellular proliferation capacity and expressed significantly higher levels of messenger RNA (mRNA) and protein expressions of IGF-1 and IGF-1R, as compared with NC chondrocytes. Furthermore, enriched IGF-1 enhanced CH chondrocytes proliferation, up-regulated the expressions of specific genes associated with cellular proliferation and elevated the gene expression of collagen type II A1 (COL2A1). Besides, IGF-1-mediated CH chondrocytes proliferation mainly depended on the mitogen-activated protein kinase (MAPK)-ERK pathway. CONCLUSIONS IGF-1 promotes human TMJ cartilage overgrowth in the developing process of CH by enhancing chondrocytes proliferation via MAPK-ERK pathway.

The clinical and radiographic characteristics of condylar osteochondroma

Osteochondroma is one of the most common benign bone tumors, but it is rare in the mandibular condyle. The purpose of this study was to increase the clinical and radiographic cognition of osteochondroma in the mandibular condyle. Thirty-four patients with radiographic and pathologic features of unilateral condylar osteochondroma were included in this retrospective study. All cases received clinical and radiographic examinations before tumor resection. Common manifestations included facial asymmetry, hypomobility, malocclusion, joint dysfunctions, and even external auditory canal stenosis. Osteochondroma might arise on the different condylar areas, such as the medial aspects (55.9%), anterior-superior (11.8%), posterior-superior (11.8%), lateral (8.8%), and generally enlarged (11.8%). The tumor formed a pseudojoint under the anterior eminence in 55.9%; the affected mandible presented normal shape in 58.8%; and horizontal mandibular deviation was caused by the tumor or elongated ramus in 70.6%. The condylar osteochondroma may locate in different positions encircling the condyle, which increases recognition and diagnosis of these lesions.

The Pilot Study of Fibrin with Temporomandibular Joint Derived Synovial Stem Cells in Repairing TMJ Disc Perforation

TMJ disc related diseases are difficult to be cured due to the poor repair ability of the disc. TMJ-SDSCs were ideal cell sources for cartilage tissue engineering which have been widely used in hyaline cartilage regeneration. Fibrin gel has been demonstrated as a potential scaffold for neocartilage formation. The aim of this study was to repair the TMJ disc perforation using fibrin/chitosan hybrid scaffold combined with TMJ-SDSCs. Rat TMJ-SDSCs were cultured on hybrid scaffold or pure chitosan scaffolds. The cell seeding efficiency, distribution, proliferation, and chondrogenic differentiation capacity were investigated. To evaluate the in vivo repair ability of cell/scaffold construct, rat TMJ disc explants were punched with a defect to mimic TMJ disc perforation. Cell seeded scaffolds were inserted into the defect of TMJ disc explants and then were implanted subcutaneously in nude mice for 4 weeks. Results demonstrated that fibrin may improve cell seeding, proliferation, and chondrogenic induction in vitro. The in vivo experiments showed more cartilage ECM deposition in fibrin/chitosan scaffold, which suggested an enhanced reparative ability. This pilot study demonstrated that the regenerative ability of TMJ-SDSCs seeded in fibrin/chitosan scaffold could be applied for repairing TMJ disc perforation.

The expressions of IGF-1, BMP-2 and TGF-β1 in cartilage of condylar hyperplasia

Condylar hyperplasia is a complex post-natal growth abnormality of the mandible and condyle, which leads to facial asymmetry. We investigated the distributions of insulin-like growth factors (IGF-1), bone morphogenetic protein-2 (BMP-2) and transforming growth factor-β1 (TGF-β1) in cartilage of condylar hyperplasia and revealed relationships between age and the cartilaginous thickness. Twenty patients with condylar hyperplasia were divided into four histopathological types. The cartilaginous thickness and age in different histological types were analysed, and the localizations of IGF-1, BMP-2 and TGF-β1 were detected by immunohistochemistry analysis. The cartilaginous thickness of condylar hyperplasia significantly increased. The cartilaginous thickness of type III was significantly thicker than type I and type II, Bivariate correlation revealed a significant correlations between age and the cartilaginous thickness (r = 0·68, P = 0·01). However, the expressions of IGF-1, BMP-2 and TGF-β1 were the strongest in type I. In almost all types of condylar hyperplasia, the presence of IGF-1 and BMP-2 was found mainly in the proliferative chondrocyte layer and the hypertrophic chondrocyte layer, and only a few in the calcified chondrocyte layer. The presence of TGF-β1 widely distributed from the fibrous articular surface to the calcified cartilage. These findings suggest that the proliferative activity of cartilage in condylar hyperplasia is strongly associated with age and cartilaginous thickness. Therefore, the four pathological types of condylar hyperplasia seem more likely to be four discontinuous stages.

Osteoarthritic Changes After Superior and Inferior Joint Space Injection of Hyaluronic Acid for the Treatment of Temporomandibular Joint Osteoarthritis With Anterior Disc Displacement Without Reduction: A Cone-Beam Computed Tomographic Evaluation

PURPOSE This study compared the effect of superior and inferior joint space injections of hyaluronic acid (HA) and evaluated osteoarthritic changes in patients diagnosed with temporomandibular joint (TMJ) anterior disc displacement without reduction (ADDw/oR) in association with osteoarthritis (OA) by cone-beam computed tomography (CBCT). MATERIALS AND METHODS One hundred forty-one patients with research diagnostic criteria for ADDw/oR in association with TMJ OA were randomly assigned to 1 of 2 study groups that received superior or inferior joint space injection of HA. CBCT and clinical examination were performed before treatment and at 3 and 9 months after treatment. RESULTS One hundred twenty-six patients returned for the 3-month evaluations, and 74 returned for the 9-month evaluations. Condylar remodeling and TMJ function showed improvement in most patients after treatment. At 3 months, remodeling scores in the superior and inferior groups were 2.14 ± 3.16 and 4.08 ± 3.82, respectively, and scores were 4.80 ± 3.36 and 7.47 ± 3.90 at 9 months. There were significant differences between the superior and inferior groups at 3 and 9 months after treatment (3-month, P = .002; 9-month, P = .002). The Helkimo index of the inferior group was significantly lower than that of superior group at 3 and 9 months (3-month, P = .008; 9-month, P = .028). There were no significant differences in maximal mouth opening between the 2 groups at 3 and 9 months (3-month, P = .82; 9-month, P = .20). CONCLUSION Superior and inferior joint space injections of HA are effective methods for the treatment of ADDw/oR in association with TMJ OA. The injection of HA within the inferior joint space appears to result in better condylar reparative remodeling and improvement in jaw function.

A retrospective study of temporomandibular joint ankylosis secondary to surgical treatment of mandibular condylar fractures

We investigated the incidence of ankylosis of the temporomandibular joint (TMJ) after open operations for fractures of the mandibular condyle, and analysed possible risk factors in a total of 385 patients with 492 condylar fractures who had been operated on in our department from 2001 to 2010. Sixteen patients developed postoperative ankylosis of the TMJ with 26 joints (5%) affected during a follow-up of 6 months-10 years. Of the 492 condylar fractures, the most common ones that were associated with postoperative ankylosis were those of the condylar head (20/248), followed by the condylar neck (6/193). Subcondylar fractures did not cause postoperative ankylosis (0/51). Among the 16 patients with postoperative ankylosis, 13 had associated anterior mandibular fractures. Long-screw (bicortical screw) fixation of fractures of the condylar head seemed to be associated with a lower incidence of postoperative ankylosis than fixation by miniplate and wire or removal of the fractured fragment. The articular discs were damaged in all ankylosed joints, and the remaining fractured fragment was found in 10 ankylosed joints after fractures of the condylar head. The results suggest that fractures of the condylar head are more prone to lead to postoperative ankylosis of the TMJ, and that the possible risk factors seem to include the technique used for fixation and damage to the disc, together with an anterior mandibular fracture with the fractured fragment remaining.

Histological evaluation of condylar hyperplasia model of rabbit following distraction osteogenesis of the condylar neck

Condylar hyperplasia is the excessive unilateral growth of mandibular leading to facial asymmetry, occlusal disturbance, joint pain and dysfunction. The aim of this study is to evaluate the histological presence of temporomandibular joint in model of condylar hyperplasia by lengthening unilateral condylar neck of distraction osteogenesis. An extra oral distractor was employed to achieve unilateral condylar neck distraction (1·0 mm daily for 7 days). The experimental condylar necks were elongated by 7 mm compared to the contralateral. Eleven adult white rabbits were used. Eight rabbits were, respectively, sacrificed after the post-distraction period (4 or 8 weeks). All animals were evaluated clinically and histomorphometrically. The condyles radiologically showed remodelling, flattening and sclerosis. In 4-week group, thinning of the cartilage was evident, and the trabeculae were long, not multiply connected. A thin, dense fibrous layer covered all over the surface of cartilage. In 8-week group, the cartilaginous layer was similar to thickness of the normal cartilage, but still thinner than control. However, the fibrous layers covering condyle manifested slight degenerative changes, and even depressions and erosions were seen in the cartilage and subchondral bone. The trabeculae showed denser and multiply connected. In 8-week group, the cartilaginous thickness of surgical condyles was significantly thinner than the contralateral. This study indicates that unilateral distraction of condylar neck loads the condyles asymmetrically. Asymmetrical loads affect more on the surgical condyles than the contralateral, and after 8 weeks of the post-distraction, condyle could recover from asymmetrical loads in some degree.

Up-regulation of proteoglycan 4 in temporomandibular osteoarthritic synovial cells by hyaluronic acid

BACKGROUND Hyaluronic acid (HA) injection is widely used in the treatment of temporomandibular joint (TMJ) osteoarthritis (OA). Proteoglycan 4 (PRG4) is another joint lubricant that protects surface of articular cartilage. But few studies had explored the role of HA in regulation of PRG4 expression in TMJ OA. In this study, the effects of HA on the expression of PRG4 in osteoarthritic TMJ synovial cells were investigated in hypoxia, which was similar to the TMJ physiologically. METHODS Synovial cells were isolated from the TMJ OA patients and were treated with or without HA under normoxia or hypoxia for indicated time periods. The proliferation of synovial cells was measured using Cell Counting Kit-8 (CCK-8). The gene expression of HAS2, VEGF, and PRG4 was detected by quantitative real-time PCR, and the secretion of PRG4 and VEGF was assayed by enzyme-linked immunosorbent assay (ELISA). Immunofluorescence was used to examine the protein expression of hypoxia-induced factor-1α (HIF-1α). RESULTS Hyaluronic acid markedly increased the proliferation of osteoarthritic synovial cells in hypoxia. The expression of HAS2 and PRG4 mRNA of osteoarthritic synovial cells under hypoxia was enhanced by HA treatment. However, HA had no effect on reducing the VEGF and HIF-1α expression in synovial cells in hypoxia. CONCLUSIONS Hyaluronic acid could promote the expression of HAS2 and PRG4, but could not modulate HIF-1α and VEGF expression of TMJ osteoarthritic synovial cells in hypoxia.