Bioinformatics analysis of miRNA and mRNA expression profiles to reveal the key miRNAs and genes in osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is a chronic degenerative joint disease and the most frequent type of arthritis. This study aimed to identify the key miRNAs and genes associated with OA progression. METHODS: The GSE105027 (microRNA [miRNA/miR] expression profile; 12 OA samples and 12 normal samples) and GSE48556 (messenger RNA [mRNA] expression profile; 106 OA samples and 33 normal samples) datasets were selected from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and miRNAs (DEMs) were analyzed using the limma and ROCR packages in R, respectively. The target genes that negatively correlated with the DEMs were predicted, followed by functional enrichment analysis and construction of the miRNA-gene and miRNA-transcription factor (TF)-gene regulatory networks. Additionally, key miRNAs and genes were screened, and their expression levels were verified by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). RESULTS: A total of 1696 DEGs (739 upregulated and 957 downregulated) and 108 DEMs (56 upregulated and 52 downregulated) were identified in the OA samples. Furthermore, 56 target genes that negatively correlated with the DEMs were predicted and found to be enriched in three functional terms (e.g., positive regulation of intracellular protein transport) and three pathways (e.g., human cytomegalovirus infection). In addition, three key miRNAs (miR-98-5p, miR-7-5p, and miR-182-5p) and six key genes (murine double minute 2, MDM2; glycogen synthase kinase 3-beta, GSK3B; transmembrane P24-trafficking protein 10, TMED10; DDB1 and CUL4-associated factor 12, DCAF12; caspase 3, CASP3; and ring finger protein 44, RNF44) were screened, among which the miR-7-5p → TMED10/DCAF12, miR-98-5p → CASP3/RNF44, and miR-182-5p → GSK3B pairs were observed in the regulatory network. Moreover, the expression levels of TMED10, miR-7-5p, CASP3, miR-98-5p, GSK3B, and miR-182-5p showed a negative correlation with qRT-PCR verification. CONCLUSION: MiR-98-5p, miR-7-5p, miR-182-5p, MDM2, GSK3B, TMED10, DCAF12, CASP3, and RNF44 may play critical roles in OA progression.

Influence of biological scaffold regulation on the proliferation of chondrocytes and the repair of articular cartilage.

PURPOSE: To investigate the effects of hard tissue engineering scaffold (the material is ß-TCP) with different micro-structures on the proliferation of chondrocytes, and the influence of its composite erythrocytes on the repair of articular cartilage defects. METHODS: Rabbit cartilage cells were on ß-TCP bioceramic scaffold with different micro-structures in vitro, the proliferation growth trend of chondrocytes within the scaffold was calculated, and a optimal micro-structure suitable for cartilage cell growth was determined. Composite chondrocytes were implanted into rabbit models of articular cartilage defects, and the repair situation was observed. RESULTS: the bioceramic scaffold with an inner diameter of 120 µm and an aperture of 500-630 µm was suitable for the growth of cartilage cells. Scaffold loaded with second generation of cartilage cell suspension got a top histological score of 20.76±2.13, which was closely similar to that of normal cartilage. CONCLUSION: When loaded with the second generation of cartilage cells, the ß-TCP biological ceramic scaffold with a pore size of 500-630 µm, and an inner diameter of 120 µm, shows a best repairing effect on animal articular cartilage defects.

An Alternative Intraoperative Radiographic Method for Optimizing Cup Inclination during Total Hip Arthroplasty.

OBJECTIVE: During total hip arthroplasty (THA), the location of the acetabular prosthesis is very important for guaranteeing successful surgery. However, this remains a challenge for many surgeons. This study aimed to investigate the feasibility of using the intraoperative fluoroscopic iliopubic tangential angle (IPTA) to determine the valgus angles of acetabular prostheses. METHODS: In the first stage, the IPTA and valgus angles of native acetabula were defined and measured in 102 THAs obtained from the picture archiving and communication systems of our hospital. Obturator foramen morphology was also measured and divided into groups according to the axial length ratio. Correlations between obturator foramen morphology and IPTA and valgus angles of native acetabula were then determined. In the second stage, angular differences (angle θ) between the IPTA and valgus angles of native acetabula were measured during unilateral THA in 136 patients to determine whether this is a stable value that could be used as a reference for placement of acetabular prostheses. Postoperative data such as Harris Hip Score (HHS) scores and complications were collected and evaluated. RESULTS: The average IPTA at the apex of the true acetabulum was 58.8° ± 4.1°. The average valgus angle of native acetabula was 43.1° ± 3.9° and angle θ was 15.7° ± 1.3°. Obturator foramen morphology was divided into five groups according to the axial length ratio. IPTA was closely related to obturator foramen morphology (Pearson r = 0.489, P ≈ 0.000). Angle θ was stable and independent of obturator foramen morphology. When the IPTA and angle θ were used as references for placing acetabular prostheses in 136 THAs, the average postoperative valgus angles of acetabular prostheses was 45.13° ± 4.07° and the good-to-excellent rate was 97.05%. There were no short-term complications such as fracture, dislocation or infection. The average HHS score 6 months after surgery was 37.2 higher than the preoperative score, this difference being significant (P < 0.01). Neither infection nor dislocation was found 6 months after surgery. CONCLUSIONS: The IPTA (at the apex of the true acetabulum) and angle θ (obtained by intraoperative fluoroscopy) are consistent in determining the postoperative valgus angle of acetabular prosthesis during THA. Thus, IPTA and angle θ are of value in guiding placement of acetabular prostheses; in particular, this method can facilitate the learning of young surgeons.

[Study on the Structure and Nanomechanical Properties of Organic Montmorillonite Reinforced Urea-Formaldehyde Adhesive].

Montmorillonite (MMT) is a natural mineral that has great potential as reinforcing filler in wood adhesives. In order to study the reinforcing mechanism more clearly, organic MMT-reinforced urea-formaldehyde adhesive (UF-OMMT) was prepared to analyze its chemical properties and crystal structure with Fourier Transform Infrared Spectroscopy (FTIR) and X-Ray Diffraction (XRD). The nanomechanical properties of UF, UF-MMT and PF-OMMT adhesives in the interphase of wood-based composite were analyzed by nanoindentation (NI) and the macro-bonding strength of composite were also tested. The results of FTIR and XRD indicated that in the spectra of MMT modified by cetyltrimethyl ammonium bromide (CTAB), the new peaks appeared at 2 929 and 2 853 cm-1corresponding to C­H stretching vibrations of the organic intercalation agent (CTAB). The (001) diffraction peak of MMT was shifted to a lower angle and the lamellar repeat distance increases from 1.51 nm to 2.71 nm after organic modification. The ion exchange of the cations in montmorillonite with organic ammonium ions and the separating and disorder crystalline improved the compatibility of the modified clay with the polymers and the dispersion of the layers into the matrix. The good physical filling of MMT particles and the elastomer formed during the reaction could transfer and distribute loads between components more homogenously, therebycontributing to the improved mechanical properties of adhesives. As compared to the untreated UF, the reduced elastic modulus and hardness of UF-OMMT in the interphase increased by about 66.9% and 24.2%, respectively. At the macroscale, the bonding strength of plywood bonded with UF-OMMT increased by about 97% as compared to that of unmodified UF resin. The positive effects of montmorillonite on water and heat resistance can be attributed to the better barrier properties of the interphase.

HDAC5 promotes osteosarcoma progression by upregulation of Twist 1 expression.

Histone deacetylases (HDACs) form a family of enzymes, which have fundamental roles in the epigenetic regulation of gene expression and contribute to the growth, differentiation, and apoptosis of cancer cells. In this study, we firstly investigated the biological function of HDAC5 in osteosarcoma cells. We found that mRNA and protein levels of HDAC5 were upregulated in osteosarcoma tissues and cell lines. Furthermore, overexpression of HDAC5 could promote cell proliferation in osteosarcoma cell lines. In contrast, HDAC5 knockdown using small interfering RNA inhibited cell proliferation. At the molecular level, we demonstrated that HDAC5 promoted mRNA expression of twist 1, which has been reported as an oncogene. Together, these results highlighted for the first time an unrecognized link between HDAC5 and osteosarcoma progression and demonstrated that its specific inhibition might contribute to the treatment of tumorigenesis.