Effects of HDAC4 on IL-1β-induced matrix metalloproteinase expression regulated partially through the WNT3A/β-catenin pathway / 中华医学杂志(英文版)

BACKGROUND@#Histone deacetylase 4 (HDAC4) regulates chondrocyte hypertrophy and bone formation. The aim of the present study was to explore the effects of HDAC4 on Interleukin 1 beta (IL-1β)-induced chondrocyte extracellular matrix degradation and whether it is regulated through the WNT family member 3A (WNT3A)/β-catenin signaling pathway.@*METHODS@#Primary chondrocytes (CC) and human chondrosarcoma cells (SW1353 cells) were treated with IL-1β and the level of HDAC4 was assayed using Western blotting. Then, HDAC4 expression in the SW1353 cells was silenced using small interfering RNA to detect the effect of HDAC4 knockdown on the levels of matrix metalloproteinase 3 (MMP3) and MMP13 induced by IL-1β. After transfection with HDAC4 plasmids, the overexpression efficiency was examined using Real-time quantitative polymerase chain reaction (qRT-PCR) and the levels of MMP3 and MMP13 were assayed using Western blotting. After incubation with IL-1β, the translocation of β-catenin into the nucleus was observed using immunofluorescence staining in SW1353 cells to investigate the activation of the WNT3A/β-catenin signaling pathway. Finally, treatment with WNT3A and transfection with glycogen synthase kinase 3 beta (GSK3β) plasmids were assessed for their effects on HDAC4 levels using Western blotting.@*RESULTS@#IL-1β downregulated HDAC4 levels in chondrocytes and SW1353 cells. Furthermore, HDAC4 knockdown increased the levels of MMP3 and MMP13, which contributed to the degradation of the extracellular matrix. Overexpression of HDAC4 inhibited IL-1β-induced increases in MMP3 and MMP13. IL-1β upregulated the levels of WNT3A, and WNT3A reduced HDAC4 levels in SW1353 cells. GSK-3β rescued IL-1β-induced downregulation of HDAC4 in SW1353 cells.@*CONCLUSION@#HDAC4 exerted an inhibitory effect on IL-1β-induced extracellular matrix degradation and was regulated partially by the WNT3A/β-catenin signaling pathway.

Chronic inflammation deteriorates structure and function of collagen fibril in rat temporomandibular joint disc / 国际口腔科学杂志·英文版

Collagen is the building component of temporomandibular joint (TMJ) discs and is often affected by inflammation in temporomandibular disorders. The macromechanical properties of collagen are deteriorated by chronic inflammation. However, the mechanism by which inflammation influences disc function remains unknown. The relationship between the ultrastructure and nanomechanical properties of collagen in inflamed discs should be clarified. Seven-week-old female Sprague-Dawley rats were randomly divided into two groups. Chronic TMJ inflammation was induced by intra-articular injection of complete Freund's adjuvant, and samples were harvested after 5 weeks. Picrosirius staining revealed multiple colours under polarized light, which represented alternative collagen bundles in inflamed discs. Using atomic force microscopy scanning, the magnitude of Young's modulus was reduced significantly accompanied with disordered collagen fibril arrangement with porous architecture of inflamed discs. Transmission electron microscopy scanning revealed a non-uniform distribution of collagen fibres, and oversized collagen fibrils were observed in inflamed discs. Fourier transform infrared microspectroscopy revealed a decrease in 1 338 cm/amide II area ratio of collagen in different regions. The peak positions of amide I and amide II bands were altered in inflamed discs, indicating collagen unfolding. Our results suggest that sustained inflammation deteriorates collagen structures, resulting in the deterioration of the ultrastructure and nanomechanical properties of rat TMJ discs.

Association between ADAMTS14 gene polymorphism and the temporomandibular joint osteoarthritis in Chinese Han females / 北京大学学报(医学版)

OBJECTIVE@#To investigate the association between single nucleotide polymorphisms (SNP) of ADAMTS14 gene rs4747096 and osteoarthritis of the temporomandibular joint in Chinese Han females.@*METHODS@#As a case-control study, a total of 213 Chinese Han females were involved in the present study, which contained 103 temporomandibular joint osteoarthritis patients and 110 healthy people who had no symptoms or signs of temporomandibular joint osteoarthritis as control. Peripheral blood samples were collected from each participant. Genomic DNAs of temporomandibular joint osteoarthritis patients and healthy control were extracted from peripheral venous blood, which were stored in -80 °C refrigerator by using DNA extraction kits. The designed primers were used for polymerase chain reaction (PCR) amplification of specific DNA fragments. Genotype was determined by sequencing the PCR products. The software Chromas 2.22 was used to analyze the genotype. The genotype distributions, allele frequencies and genetic models between the patients and controls were compared. The age distribution was checked by t-test. Genotype and allele frequency were detected by Chi-square test.@*RESULTS@#In the present study, there were no significant differences between the osteoarthritis patients and healthy controls in terms of age. The genotype distribution was in accordance with Hardy-Weinberg equilibrium in the two groups. The genotype frequency of the ADAMTS14 (rs4747096) in the experimental group was 38.8% (AA), 55.4% (AG), and 5.8% (GG), respectively. The genotype frequency in the control group was 40.9% (AA), 43.6% (AG), and 15.5% (GG), respectively. The difference of genotype frequency of the ADAMTS14 (rs4747096) was significant between the experimental group and the control group (P=0.047). There was no significant difference in allele frequency between the two groups (P=0.415). AA and AG genotypes significantly increased the risk of the disease compared with GG in dominant model (OR=1.114, 95% CI: 1.015-1.223, P=0.028).@*CONCLUSION@#A significant correlationship was found between the ADAMTS14 (rs4747096) SNP and the temporomandibular joint osteoarthritis in Chinese Han females. The distribution of rs4747096 may be different between temporomandibular joint osteoarthritis and healthy population.