High mobility group 1 protein (HMGB1), a highly conserved nuclear DNA-binding protein and inflammatory mediator, has been recently found to be involved in angiogenesis. Our previous study has demonstrated the elevation of HMGB1 in the tissue of perforated disc of temporomandibular joint (TMJ). Here, we investigated a novel mediator of HMGB1 in regulating hypoxia-inducible factor-1a (HIF-1a) and vascular endothelial growth factor (VEGF) to mediate angiogenesis in perforated disc cells of TMJ. HMGB1 increased the expression of HIF-1a and VEGF in a dose-and time-dependent manner in these cells. Moreover, immunofluorescence assay exhibits that the HIF-1a were activated by HMGB1. In addition, HMGB1 activated extracellular signal-related kinase 1/2 (Erk1/2), Jun N-terminal kinase (JNK), but not P38 in these cells. Furthermore, both U0126 (ErK inhibitor) and SP600125 (JNK inhibitor) significantly suppressed the enhanced production of HIF-1a and VEGF induced by HMGB1. Tube formation of human umbilical vein endothelial cells (HUVECs) was significantly increased by exposure to conditioned medium derived from HMGB1-stimulated perforated disc cells, while attenuated with pre-treatment of inhibitors for VEGF, HIF-1a, Erk and JNK, individually. Therefore, abundance of HMGB1 mediates activation of HIF-1a in disc cells via Erk and JNK pathway and then, initiates VEGF secretion, thereby leading to disc angiogenesis and accelerating degenerative change of the perforated disc.

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Keywords:MiR-15b Condylar hyperplasia IGF1 IGF1R BCL2 s u m m a r yObjective: This study aimed to explore potential microRNAs (miRNAs), which participate in the pathological process of condylar hyperplasia (CH) through targeting specific proliferation-and apoptosisrelated genes of chondrocytes. Methods: Insulin-like growth factor 1 (IGF1), IGF1 receptor (IGF1R) and B-cell CLL/lymphoma 2 (BCL2) in CH cartilage were detected by real-time polymerase chain reaction (PCR), Western blot, immunohistochemistry and immunofluorescence. MiRanda and TargetScanS algorithms were used to predict certain miRNAs in CH chondrocytes concurrently modulating the above three genes. MiR-15b was screened and identified using real-time PCR. After transfection of miR-15b mimics or inhibitor into CH chondrocytes, expression of the above three genes was detected by real-time PCR and western blot, meanwhile, cell proliferation and apoptosis was examined by CCK8, cell cycle assays, flow cytometry and Hoechst staining. Dual luciferase activity was performed to identify the direct regulation of miR-15b on IGF1, IGF1R and BCL2. Results: Expression of IGF1, IGF1R and BCL2 increased in CH cartilage. Seven microRNAs concurrently correlated with IGF1, IGF1R and BCL2. Among them, only miR-15b significantly changed in CH chondrocytes. Overexpression of miR-15b in CH chondrocytes suppressed the expression of IGF1, IGF1R and BCL2, while it increased when miR-15b was knockdown. Furthermore, miR-15b suppressed their expression by directly binding to its 3 0 -UTR in these cells. Besides, miR-15b hampered chondrocytes proliferation through targeting IGF1 and IGF1R and accelerated chondrocytes apoptosis through targeting BCL2. Conclusion: Suppressed miR-15b contributed to enhanced proliferation capacity and weakened apoptosis of chondrocytes through augmentation of IGF1, IGF1R and BCL2, thereby resulting in development of CH.

Synovitis contributes to temporomandibular joint (TMJ) pain, nevertheless, the detailed nociceptive mechanism remains unclear. In this study, a rat model of TMJ synovitis was induced by intra-articular injection with complete Freund's adjuvant (CFA). After CFA-induced synovitis, pain behaviors were observed. Then, TMJ, trigeminal ganglion, and trigeminal nucleus caudalis (TNC) tissues were collected, and immunohistochemistry was used to detect the expression of substance P (SP) and protein gene product 9.5 (PGP9.5) in the synovium tissue. Furthermore, the gene expression level of SP and PGP9.5 in synovium was detected by reverse transcription-polymerase chain reaction (RT-PCR). Afterwards, the expression of SP in the trigeminal ganglion and TNC and c-fos in the TNC was detected by immunohistochemistry. Compared with the control group, the expression of SP and PGP9.5 nerve fibers density and gene levels of them in the synovium tissue were significantly increased in CFA-induced TMJ synovitis rats. Similarly, SP expression in the trigeminal ganglion and TNC, and c-fos expression in the TNC were also obviously increased in CFA-induced TMJ synovitis rats. Collectively, CFA-induced rat TMJ synovitis resulted in obvious pain. This nociceptive reaction could be attributed to the augmented quantity of SP and PGP9.5 positive-stained nerve fibers distributed in the inflammatory synovium as well as enhanced SP expression in the trigeminal ganglion and TNC tissue. c-fos expression in the rat TNC illustrates CFA-induced TMJ synovitis can evoke the acute pain.

No abstract

Background: Synovial chondromatosis (SC) of temporomandibular joint (TMJ) occupies 3% SC cases. In other joints like hip and knee which were composed hyaline cartilage (HC), loose bodies (LBs) were reported to be a HC feature. However, condyle surface and disc in TMJ are fibrous cartilage (FC). Therefore, we proposed a different pathogenesis of TMJSC.Methods: LBs and synovium were collected from seven TMJSC patients, and histological and immunohistological examinations were performed.Results: Three ways of HC formation were discovered: regular-shaped cartilaginous nodules (CNs) in sublining layer (SL) of vascularized synovium, regional chondrification of SL, and finger-like tissue with a tail attaching to synovium. Detached LBs could fuse and were only positively stained by aggrecan. Without synovium attachment to LBs, fused LBs remained a hyaline extracellular matrix (ECM). However, after synovium attachment, transformation from HC to FC occurred. Two types of FC were observed. First type FC was featured by vertical-distributed type I collagen fibers imbedding few chondrocytes, suggesting mature phase with superior mechanical features. Second type FC was featured by medium-density chondrocytes with type I collagen and aggrecan-positive ECM, suggesting primary phase. The transformation process started in appearance of 2nd type FC deriving from synovium covering LB, and gradually replaced HC from periphery to center. Conclusions: Three ways of HC formation were closely related. Different with SC in other joints, hyaline ECM in LBs of TMJSC could be replaced by FC deriving from synovium, during which 2nd type FC first replaced HC and then transformed to 1st type FC. K E Y W O R D S angiogenesis, fibrous cartilage, hyaline cartilage, loose bodies, synovial chondromatosis 1 | INTRODUCTION Synovial chondromatosis (SC) is an uncommon, benign and proliferative disorder of subsynovial cartilaginous metaplasia. 1 It is characterized by formation of hyaline cartilaginous nodules (CNs) in sublining layer (SL) of synovium, subsequently separation from synovium and formation of loose bodies (LBs) in joint compartment. 2 Though large joints such as knee, elbow, and hip are usually affected by SC, 3 SC in temporomandibular joint (TMJ) only occupies 3% cases. 4 More than 200 cases of TMJSC had been presented in literatures. 5 The existence of LBs in TMJ causes joint pain, limited mouth opening and degenerative changes for disc, condyle and glenoid fossa 6 even skull base, 7 which impedes normal function of TMJ.

Background This study aimed to quantify the morphological changes of temporomandibular joint (TMJ) discs after disc repositioning surgery using the three-dimensional (3D) modeling. Methods Thirty patients who diagnosed with unilateral ADDwoR were included to compare the morphological differences between ADDWoR discs and normal discs, and fifteen patients who experienced unilateral or bilateral disc repositioning surgery were included to analyze the morphological changes before and after disc repositioning surgery. Disc 3D reconstruction and analyses were performed using magnetic resonance imaging (MRI) data. Results In the unilateral ADDwoR patients, volume, superficial area, length, and maximum longitudinal-sectional area of the ADDwoR disc were significantly smaller compared with the non-affected discs. However, there was no significant difference in width and cross-sectional areas between ADDwoR discs and non-affected discs. In patients who subjected to disc repositioning surgery, disc volume, superficial area, length, width and maximum longitudinal-sectional area of TMJ discs were markedly increased 6 months after surgery. Conclusions This study demonstrated that the TMJ discs tended to be morphologically smaller in volume and shorter in length under ADDwoR status. Importantly, the ADDwoR discs tended to morphologically recover toward non-affected discs after 6 months follow-up following TMJ disc repositioning surgery.

Three-dimensional (3D) printed implants have attracted substantial attention in the field of personalized medicine, but negative impacts on mechanical properties or initial osteointegration have limited their application. To address these problems, we prepared hierarchical Ti phosphate/Ti oxide (TiP-Ti) hybrid coatings on 3D printed Ti scaffolds. The surface morphology, chemical composition, and bonding strength of the scaffolds were characterized by scanning electron microscopy (SEM), atomic force microscopy (AFM), contact angle measurement, X-ray diffraction (XRD), and scratch test. In vitro performance was analyzed by colonization and proliferation of rat bone marrow mesenchymal stem cells (BMSCs). In vivo osteointegration of the scaffolds in rat femurs was assessed by micro-CT and histological analyses. The results demonstrated improved cell colonization and proliferation as well as excellent osteointegration obtained by incorporation of our scaffolds with the novel TiP-Ti coating. In conclusion, micron/submicron scaled Ti phosphate/Ti oxide hybrid coatings on 3D printed scaffolds have promising potential in future biomedical applications.