LncRNA PVT1 induces chondrocyte apoptosis through upregulation of TNF-α in synoviocytes by sponging miR-211-3p.

Temporomandibular joint osteoarthritis (TMJ OA) is an important subtype of temporomandibular disorders (TMD). Articular cartilage destruction is considered a common pathological feature of TMJ OA, which is reported to be mainly induced by chondrocyte apoptosis. Synovial sterile inflammation is an initial factor of TMJ OA-associated articular cartilage destruction. Therefore, determining the mechanism of synovial membrane inflammation-induced articular cartilage destruction in TMJ OA is important for the TMJ OA therapy. In this study, we detected the function of synoviocytes in chondrocyte apoptosis under lipopolysaccharide (LPS)-induced inflammatory conditions and explored the underlying mechanism. We found that synoviocytes in inflammatory conditions facilitated LPS-induced chondrocytes apoptosis by secreting increased Tumor Necrosis Factor α (TNF-α), which was induced by long non-coding RNA plasmacytoma variant translocation 1 (PVT1) upregulation. PVT1 served as a competing endogenous RNA that sponged the microRNA miR-211-3p and prevented the inhibition of TNF-α expression. In conclusion, our in vitro study revealed that PVT1 has a previously unknown role in chondrocyte apoptosis, which may also be a mechanism underlying synoviocyte involvement in TMJ OA.

Condylar and occlusal changes after high condylectomy and orthodontic treatment for condylar hyperplasia.

Condylar hyperplasia (CH) of human temporomandibular joint (TMJ) often occurs unilaterally, and causes occlusal disturbance and facial asymmetry. The purpose of this study was to compare the effects of high condylectomy with and without postsurgical orthodontic treatment. Forty patients were diagnosed as having active CH and treated with high condylectomy. Patients in group A (n=24) took the postsurgical orthodontic therapy immediately after surgery, and those in group B (n=16) did not take orthodontic therapy. For both groups, the mandibular ramus height on the affected side was decreased significantly after surgery. Orthodontic treatment promoted maxillary alveolar remodeling significantly by depressing alveolar bone of the affected side and increasing alveolar bone of the nonaffected side. Better improvement for facial midline deviations was observed in group A than in group B. In both groups, the condylar remodeling was observed and manifested by the smoothening of condylar surface and returning of condyle to normal position in glenoid fossa. It was concluded that high condylectomy in the treatment of active CH of TMJ improved the functional occlusion and facial aesthetic. Postsurgical orthodontic therapy could more effectively enhance maxillary alveolar and condylar remodeling, and more rapidly and meticulously establish the stable occlusal and normal position of condyle than the spontaneous remodeling.

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.

A hypothetical biological synovial fluid for treatment of temporomandibular joint disease.

Temporomandibular Joint disorder (TMD) is a common disorder of mandibular motion system with distinct clinicopathological characteristics. TMD may cause to change in the components of synovial fluid, that affects the functions on lubrication and nutrition of cartilage. Boundary lubrication system contributing to the low friction of joint consists of three parts: lubricin, surface-active phospholipids and hyaluronan (HA). Diminishment of lubrication function is thereby implicated as an adverse contributing factor in degenerative joint diseases such as internal derangement, osteoarthrosis. Moreover, mesenchymal stem cells (MSCs) of synovial membrane can be obtained without irreversible damage, are easily expandable with limited senescence. We postulate that biological active components secreted from MSCs are separated and accumulated by gel permeation chromatography, and then we use the ultra-flirtation of serum and biologically active components to reconstruct the biological synovial fluid in order to rehabilitate the boundary lubrication system and the nutrition of cartilage. Further study investigating the components of biological synovial fluid provides with new treatment strategy for TMD.

Regulation of HAS expression in human synovial lining cells of TMJ by IL-1beta.

Hyaluronan (HA), a major glycosaminoglycan of synovial fluid, is synthesised by a class of membrane-bound HA synthase (HAS) proteins. In the present study, we investigated the regulatory roles of IL-1beta on HAS gene expression and HA production by the fibroblastic synovial lining cells. The synovial lining cells from synovial membrane in human temporomandibular joint (TMJ) were cultured and characterised using immunocytochemistry with CD14, CD44, and vimentin monoclonal antibodies. With or without treatment with IL-1beta, the production of HA was detected with radiometric assay and the expression of HAS mRNAs were analysed with a semi-quantitative reverse transcribed polymerase chain reaction (RT-PCR). HA synthesis was significantly augmented with 1ng/ml of IL-1beta for both 24 and 48h stimulation, however the production of HA declined if stimulated with 10ng/ml of IL-1beta. The expression of HAS2 and 3 mRNA were enhanced about 4.2- and 7.2-fold after 4h stimulation with 1ng/ml of IL-1beta, respectively. From these results, it is concluded that IL-1beta functions on regulating HAS expression and consequently promoting the secretion of HA in synovial lining cells from TMJ.

[Identification and characterization of synovial mesenchymal stem cells in temporomandibular joint].

OBJECTIVE: To identify and characterize mesenchymal stem cells from synovial membrane of temporomandibular joint in vitro. METHODS: Synovial mesenchymal stem cells (SMSCs) were obtained by limited dilution method and expanded in 25 ml flasks. Methyl thiazolyl tetrazolium (MTT) method was used to determine the cell growth cycles. The expressions of vimentin and keratin were respectively detected with immunocytochemistry, while the expressions of CD8, CD34, CD44, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) were determined by flow cytometry. RESULTS: Pure mesenchymal stem cells were of spindle shape and uniform in size, which were intensively positive in vimentin, but negative in keratin. The expression of CD44, VCAM-1 and ICAM-1 were also verified by flow cytometry. CONCLUSIONS: Mesenchymal stem cells could be purified from adult synovial membrane of temporomandibular joint.

[The role of hypoxia on expression of cyclooxygenase-2 in synovial fibroblasts derived from human temporomandular joint].

OBJECTIVE: To investigate the effects of hypoxia on expression of COX-2 in synovial fibroblasts derived from human TMJ and to analyze the biological role of COX-2 on TMJ disorders. METHODS: Synovial fibroblasts were induced by hypoxia, COX-2 expression was determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. Moreover, cells were stimulated by hypoxia or celecoxib or both of them, prostaglandin E(2) (PGE(2)), matrix metalloproteinase 2, 9 (MMP-2, MMP-9) release was detected by enzyme-linked immunosorbent assay (ELISA) or gelatin zymography. Cells that were placed under normoxic conditons were used as controls. RESULTS: (1) In response to hypoxia, at 4 h (1.51 +/- 0.34), 8 h (1.39 +/- 0.57), significant elevation of COX-2 mRNA expression occurred, compared with data (0.65 +/- 0.24), (0.71 +/- 0.15) under normoxic condition (both P < 0.05). (2) The elevation of COX-2 protein was detectable at 6 h (0.29 +/- 0.06), 12 h (0.51 +/- 0.09), 24 h (0.68 +/- 0.11), contrasted with normoxia (all P < 0.01). Therefore, it is suggested that COX-2 expression pattern present a time-dependent response to hypoxic conditions. (3) The concentration of PGE(2) released by synovial fibroblasts under 12 h hypoxic condition (7.6 ng/ml +/- 0.8 ng/ml) was significantly higher than those under normoxic condition (2.5 ng/ml +/- 0.4 ng/ml, P < 0.01) or in response to celecoxib combined with hypoxia (4.3 ng/ml +/- 0.4 ng/ml, P < 0.05). (4) The amount of MMP-2, MMP-9 produced by synovial fibroblasts under 12 h hypoxic condition was upregulated compared with that under normoxia or in response to celecoxib combined with hypoxia. CONCLUSIONS: Hypoxia is, at least in part, responsible for the pathogenesis of TMJ disorders, probably by promoting COX-2 expression of synovial fibroblasts derived from TMJ.