Decreased expression of ATP-binding cassette protein G1 promotes abnormal adipogenesis of condylar chondrocytes in temporomandibular joint osteoarthritis.

BACKGROUND: Abnormal lipid metabolism is involved in the development of osteoarthritis (OA). ATP-binding cassette protein G1 (ABCG1) is crucial in mediating the outflow of cholesterol, phosphatidylcholine and sphingomyelin and reducing intracellular lipid accumulation. OBJECTIVE: This study aimed to evaluate whether ABCG1 participates in the abnormal adipogenesis of chondrocytes in osteoarthritic cartilage of temporomandibular joint. METHODS: Eight-week-old female rats were subjected to unilateral anterior crossbite (UAC) to induce OA in the temporomandibular joint (TMJ). Histochemical staining, immunohistochemical (IHC) staining, and qRT-PCR were performed. Primary condylar chondrocytes of rats were transfected with ABCG1 shRNA or overexpression lentivirus and then stimulated with fluid flow shear stress (FFSS). Cells were collected for oil red O staining, immunofluorescence staining, and qRT-PCR analysis. RESULTS: Abnormal adipogenesis, characterized by increased expression of Adiponectin, CCAAT/enhancer-binding protein α (Cebpα), fatty acid binding protein 4 (Fabp4) and Perilipin1, was enhanced in the degenerative cartilage of TMJ OA in rats with UAC, accompanied by decreased expression of ABCG1. After FFSS stimulation, we observed lipid droplets in the cytoplasm of cultured cells with increased expression of Adiponectin, Cebpα, Fabp4 and Perilipin1 and decreased expression of ABCG1. Knockdown of Abcg1 induced abnormal adipogenesis and differentiation of condylar chondrocytes. Overexpression of ABCG1 alleviated the abnormal adipogenesis and differentiation of condylar chondrocytes induced by FFSS. CONCLUSIONS: Abnormal adipogenesis of chondrocytes and decreased ABCG1 expression were observed in degenerative cartilage of TMJ OA. ABCG1 overexpression effectively inhibits the adipogenesis of chondrocytes and thus alleviates TMJ condylar cartilage degeneration.

Bioengineered Platelets Combining Chemotherapy and Immunotherapy for Postsurgical Melanoma Treatment: Internal Core-Loaded Doxorubicin and External Surface-Anchored Anti-PD-L1 Antibody Backpacks.

The pivotal factors affecting the survival rate of patients include metastasis and tumor recurrence after the resection of the primary tumor. Anti-PD-L1 antibody (aPD-L1) has promising efficacy but with some side effects for the off-target binding between aPD-L1 and normal tissues. Here, inspired by the excellent targeting capability of platelets with respect to tumor cells, we propose bioengineered platelets (PDNGs) with inner-loaded doxorubicin (DOX) and outer-anchored aPD-L1-cross-linked nanogels to reduce tumor relapse and metastatic spread postoperation. The cargo does not impair the normal physiological functions of platelets. Free aPD-L1 is cross-linked to form nanogels with a higher drug-loading efficiency and is sustainably released to trigger the T-cell-mediated destruction of tumor cells, reversing the tumor immunosuppressive microenvironment. PDNGs can reduce the postoperative tumor recurrence and metastasis rate, prolonging the survival time of mice. Our findings indicate that bioengineered platelets are promising in postsurgical cancer treatment by the tumor-capturing and in situ microvesicle-secreting capabilities of platelets.

The effect of 3D-printed plastic teeth on scores in a tooth morphology course in a Chinese university.

BACKGROUND: The tooth morphology course is an important basic dental course. However, it is difficult to fully reflect the three-dimensional (3D) morphological characteristics of tooth structure in two-dimensional pictures in traditional textbooks. The aim of this study was to assess the effect of 3D-printed plastic model teeth in the teaching of tooth morphology. METHODS: Twenty-two undergraduate students who matriculated at the School of Stomatology, the Fourth Medical University, in 2014 and 23 who matriculated in 2016 participated in the study. Each student who matriculated in 2016 was given a full set of fourteen standard 3D-printed plastic model teeth for use during the learning process, and an anonymous questionnaire was used to evaluate the usefulness of the 3D-printed plastic model teeth from the perspective of the students. RESULTS: There was no significant difference between the two groups in the scores of the theoretical examination or the total score. However, for the score of the sculpted gypsum teeth, the students who used the 3D-printed plastic model teeth in their studies scored significantly higher (P = 0.002). More than 90% of the students thought that the 3D-printed plastic model teeth were of great help or were very helpful for mastering the anatomy of teeth and for carving the gypsum teeth. CONCLUSION: Standard 3D-printed plastic teeth can effectively assist students in learning tooth morphology by transforming two-dimensional pictures and descriptions in the textbook into a 3D conformation, effectively promoting students' learning and mastery of tooth morphology and structure. Additionally, the results suggest that 3D-printed plastic model teeth are of great help to the students in mastering and improving their carving skills.

HMGB2 promotes chondrocyte proliferation under negative pressure through the phosphorylation of AKT.

Cells in articular cartilage are zonal arranged. Cells in superficial zone cartilage are generally small and proliferative. Appropriate negative pressure stimulation is beneficial to cell survival and tissue repair. Whether negative pressure has promotive impact on the proliferation activity of the superficial zone chondrocytes is of interest. In this study, we isolated superficial chondrocytes from the mandibular condylar cartilage of rats. After negative pressure treatment, the cells were collected for RNA-sequencing, quantitative real-time PCR and western blotting assays, aiming to detect the proliferative responses of chondrocytes to negative pressure and explore the potential molecular mechanisms. Data from RNA-sequencing analysis indicated that the superficial chondrocytes responded to the 4 h -10 kPa treatment by a significant increase in proliferation. In addition, the expression of high-mobility group box 2 (HMGB2) and the phosphorylation of AKT were obviously promoted. Knockdown of HMGB2 decreased AKT phosphorylation and diminished the negative pressure-induced proliferation of chondrocytes, as shown by decreased expression of Ki67 and cyclin-dependent kinase 6 (CDK6). In contrast, overexpression of HMGB2 enhanced AKT phosphorylation and further promoted proliferative activity. Moreover, LY294002, an AKT inhibitor, suppressed the proliferative activity of chondrocytes under negative pressure, while SC79, an activator of AKT phosphorylation, enhanced the proliferation of chondrocytes. Our data demonstrated that HMGB2 exhibits a promotion impact on chondrocyte proliferation under negative pressure via the phosphorylation of AKT. These results provide a new perspective for superficial zone chondrocytes proliferation under negative pressure, which should be benefit for cartilage regeneration.