Superior short-term outcomes of FNS in combination with a cannulated screw in treating femoral neck fractures.

BACKGROUND: This study aimed to evaluate the clinical efficacy of the femoral neck system alone or in combination with a cannulated screw compared with other internal fixation methods for treating femoral neck fractures. We further investigated the predictive effects of tip-apex distance (TAD) on clinical efficacy. METHODS: Data from 129 young adults with femoral neck fractures followed up at The Second Affiliated Hospital of Fujian Medical University between January 2016 and June 2022 were retrospectively collected. The patients were categorized into four groups based on the different internal fixation methods. Analysis and comparisons of the four group were performed according to age, ASA score, operation time, blood loss, fracture classification, fracture healing time, Harris score, TAD value, presence of complications (osteonecrosis of the femoral head, screw failure, and femoral neck shortening), and changes in the neck-shaft angle. RESULTS: All 129 patients were followed up for at least one year. The group who received treatment with the femoral neck system combined with a cannulated screw exhibited the shortest fracture healing time. Differences were observed in the change of neck-shaft angle among the four groups (P < 0.001), with the smallest change observed in the aforementioned group (0.76 ± 0.54°). The femoral neck shortening was also lower in groups with the femoral neck system or combined with a cannulated screw. At the last follow-up surgery, the combined treatment group achieved the highest HHS score. Subgroup analysis revealed that when the TAD was less than 25 and 49 mm for the femoral neck system and combined groups, respectively, there was less femoral neck shortening, less change in the neck-shaft angle, and a higher HHS score. CONCLUSIONS: The femoral neck system alone or combined with a cannulated screw demonstrated better short-term efficacy in the treatment of femoral neck fractures. Furthermore, TAD may serve as a predictive indicator of the potential success of femoral neck fracture treatment.

Long non-coding RNA plasmacytoma variant translocation 1 and growth arrest specific 5 regulate each other in osteoarthritis to regulate the apoptosis of chondrocytes.

Long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) and growth arrest specific 5 (GAS5) have opposite functions in the apoptosis of chondrocytes, which are involved in the pathogenesis of osteoarthritis (OA). The opposite roles of PVT1 and GAS5 in OA may indicate the existence of crosstalk between them in OA. This study aimed to explore the possible interaction between PVT1 and GAS5 in OA. Accumulation of PVT1 and GAS5 in OA and control synovial fluid samples was measured by RT-qPCR. The interaction between PVT1 and GAS5 in chondrocytes was explored by overexpression experiments. Dual-luciferase reporter assay was performed to analyze the binding of PVT1 and GAS5 to each other's promoter regions. Regulatory roles of PVT1 and GAS5 in the apoptosis of chondrocytes were studied with cell apoptosis assay. PVT1 was upregulated in OA, and GAS5 was downregulated in OA. An inverse correlation between PVT1 and GAS5 was observed across OA samples. Under lipopolysaccharides (LPS) treatment, PVT1 was upregulated and GAS5 was downregulated. Interestingly, PVT1 and GAS5 overexpression downregulated each other in chondrocytes. Cell apoptosis analysis showed that PVT1 overexpression promoted cell apoptosis, while GAS5 overexpression suppressed cell apoptosis induced by LPS. Co-transfection of PVT1 and GAS5 failed to significantly affect cell apoptosis. PVT1 and GAS5 directly bound to each other's promoter regions. Our study characterized the interaction between PVT1 and GAS5 in OA. Their interaction regulated the apoptosis of chondrocytes, which play a critical role in OA. PVT1 and GAS5 may form a negative feedback loop in OA.

MicroRNA-455-3p regulates proliferation and osteoclast differentiation of RAW264.7 cells by targeting PTEN.

BACKGROUND: Macrophages are one of the important cells in immune system. In this article, we aim to explore the regulatory role of miR-455-3p on proliferation and osteoblast differentiation of RAW264.7 cells. METHODS: Expression levels of genes and proteins in cells were tested via qRT-PCR and western blot. The targeted correlation between miR-455-3p and PTEN was identified by luciferase analysis. MTT assay and flow cytometry were applied to detect the proliferation and apoptosis of cells. Osteoclastogenesis was completed by stimulating RAW 264.7 cells with RANKL. Tartrate-resistant acid phosphatase (TRAP) activity in different groups of cells were assessed. RESULTS: Firstly, we determined that up-regulation of miR-455-3p promoted the proliferation and inhibited apoptosis of RAW 264.7 cells. MiR-455-3p deficiency played opposite effect in RAW 264.7 cells. Additionally, osteoclastogenesis-related factors (TRAP, CTSK and NFATc1) expression levels were remarkably up-regulated in miR-455-3p-mimic group of RAW264.7 cells treated with RANKL, but decreased in inhibitor group. Luciferase assay proved that miR-455-3p targeted PTEN. We took a further step and found overexpression of PTEN significantly inhibited the increased proliferation and osteoblast differentiation of RAW264.7 cells induced by miR-455-3p. CONCLUSIONS: Our findings supported basic to explore the molecular mechanism of proliferation and osteoblast differentiation of RAW264.7 cells.

Single-cell rna seq analysis identifies the biomarkers and differentiation of chondrocyte in human osteoarthritis.

BACKGROUND: Single-cell RNA sequencing (scRNA-seq) was recently adopted for exploring molecular programmes and lineage progression patterns of pathogenesis of important diseases. In this study, scRNA-seq was used to identify potential markers for chondrocytes in osteoarthritis (OA) and to explore the function of different types of chondrocytes in OA. METHODS: Here we aimed to identify the biomarkers and differentiation of chondrocyte by Single-cell RNA seq analysis. GeneOntology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to identify the function of candidate marker genes in chondrocytes. Protein-protein interaction (PPI) network was constructed to find the hub genes in 3 types of chondrocyte respectively. We also used qRT-PCR to detect the expression level of the candidate marker genes in different types of chondrocyte. RESULTS: In this study, we characterized the single-cell expression profiling of 480 chondrocyte samples and found hypertrophic chondrocyte (HTC), homeostatic chondrocyte (HomC) and fibrocartilage chondrocyte (FC) respectively. The results of GO and KEGG analysis showed the candidate marker genes made specific function in these chondrocytes to regulate the development of OAs respectively. We further revealed the differential expression of top 10 marker genes in 3 types of chondrocyte. The marker genes of HTC and FC were mainly expressed in their cell subset respectively. The marker genes of HomC did not have obviously differential expression among different types of chondrocyte. Last, we predicted the key genes in each cell subset. CD44, JUN and FN1 were predicted tightly related to the proliferation and differentiation of chondrocytes in OAs and could be regarded as biomarkers to estimate the development of OA. CONCLUSION: Our results provide new insights into exploring the roles of different types of chondrocyte in OA. The biomarkers of chondrocyte were also valuable for estimating OA progression.

Inhibition of leucine-rich repeats and calponin homology domain containing 1 accelerates microglia-mediated neuroinflammation in a rat traumatic spinal cord injury model.

BACKGROUND: Spinal cord injury (SCI) triggers the primary mechanical injury and secondary inflammation-mediated injury. Neuroinflammation-mediated insult causes secondary and extensive neurological damage after SCI. Microglia play a pivotal role in the initiation and progression of post-SCI neuroinflammation. METHODS: To elucidate the significance of LRCH1 to microglial functions, we applied lentivirus-induced LRCH1 knockdown in primary microglia culture and tested the role of LRCH1 in microglia-mediated inflammatory reaction both in vitro and in a rat SCI model. RESULTS: We found that LRCH1 was downregulated in microglia after traumatic SCI. LRCH1 knockdown increased the production of pro-inflammatory cytokines such as IL-1ß, TNF-α, and IL-6 after in vitro priming with lipopolysaccharide and adenosine triphosphate. Furthermore, LRCH1 knockdown promoted the priming-induced microglial polarization towards the pro-inflammatory inducible nitric oxide synthase (iNOS)-expressing microglia. LRCH1 knockdown also enhanced microglia-mediated N27 neuron death after priming. Further analysis revealed that LRCH1 knockdown increased priming-induced activation of p38 mitogen-activated protein kinase (MAPK) and Erk1/2 signaling, which are crucial to the inflammatory response of microglia. When LRCH1-knockdown microglia were adoptively injected into rat spinal cords, they enhanced post-SCI production of pro-inflammatory cytokines, increased SCI-induced recruitment of leukocytes, aggravated SCI-induced tissue damage and neuronal death, and worsened the locomotor function. CONCLUSION: Our study reveals for the first time that LRCH1 serves as a negative regulator of microglia-mediated neuroinflammation after SCI and provides clues for developing novel therapeutic approaches against SCI.