MiR-1908/EXO1 and MiR-203a/FOS, regulated by scd1, are associated with fracture risk and bone health in postmenopausal diabetic women.

BACKGROUND: Stearoyl-coenzyme A desaturase-1 (SCD1) can inhibit the development of diabetic bone disease by promoting osteogenesis. In this study, we examined whether this regulation by SCD1 is achieved by regulating the expression of related miRNAs. METHODS: SCD1 expression levels were observed in human bone-marrow mesenchymal stem cells (BM-MSCs) of patients with type 2 diabetes mellitus (T2DM), and the effect of SCD1 on osteogenesis was observed in human adipose-derived MSCs transfected with the SCD1 lentiviral system. We designed a bioinformatics prediction model to select important differentially expressed miRNAs, and established protein-protein interaction and miRNA-mRNA networks. miRNAs and mRNAs were extracted and their differential expression was detected. The SCD1-miRNA-mRNA network was validated. FINDINGS: SCD1 expression in bone marrow was downregulated in patients with T2DM and low-energy fracture, and SCD1 expression promotes BM-MSC osteogenic differentiation. The predictors in the nomogram were seven microRNAs, including hsa-miR-1908 and hsa-miR-203a. SCD1 inhibited the expression of CDKN1A and FOS, but promoted the expression of EXO1 and PLS1. miR-1908 was a regulator of EXO1 expression, and miR-203a was a regulator of FOS expression. INTERPRETATION: The regulation of BM-MSCs by SCD1 is a necessary condition for osteogenesis through the miR-203a/FOS and miR-1908/EXO1 regulatory pathways.

Predicting the risk of sarcopenia in elderly patients with patellar fracture: development and assessment of a new predictive nomogram.

PURPOSE: To develop a risk prediction model for postoperative sarcopenia in elderly patients with patellar fractures in China. PATIENTS AND METHODS: We conducted a community survey of patients aged ≥55 years who underwent surgery for patellar fractures between January 2013 and October 2018, through telephone interviews, community visits, and outpatient follow-up. We established a predictive model for assessing the risk of sarcopenia after patellar fractures. We developed the prediction model by combining multivariate logistic regression analysis with the least absolute shrinkage model and selection operator regression (lasso analysis) as well as the Support Vector Machine (SVM) algorithm. The predictive quality and clinical utility of the predictive model were determined using C-index, calibration plots, and decision curve analysis. We also conducted internal sampling methods for qualitative assessment. RESULT: We recruited 137 participants (53 male; mean age, 65.7 years). Various risk factors were assessed, and low body mass index and advanced age were identified as the most important risk factor (P < 0.05). The prediction rate of the model was good (C-index: 0.88; 95% CI [0.80552-0.95448]), with a satisfactory correction effect. The C index is 0.97 in the validation queue and 0.894 in the entire cohort. Decision curve analysis suggested good clinical practicability. CONCLUSION: Our prediction model shows promise as a cost-effective tool for predicting the risk of postoperative sarcopenia in elderly patients based on the following: advanced age, low body mass index, diabetes, less outdoor exercise, no postoperative rehabilitation, different surgical methods, diabetes, open fracture, and removal of internal fixation.

Nano-carrier mediated co-delivery of methyl prednisolone and minocycline for improved post-traumatic spinal cord injury conditions in rats.

OBJECTIVE: The objective of this study is to investigate the fate of albumin coupled nanoparticulate system over non-targeted drug carrier in the treatment of hemisectioned spinal cord injury (SCI). SIGNIFICANCE: Targeted delivery of methyl prednisolone (MP) and minocycline (MC) portrayed improved therapeutic efficacy as compared with non-targeted nanoparticles (NPS). METHODS: Albumin coupled, chitosan stabilized, and cationic NPS (albumin-MP + MC - NPS) of poly-(lactide-co-glycolic acid) were prepared using the emulsion solvent evaporation method. Prepared NPS were characterized for drug entrapment efficiency, particle size, poly-dispersity index (PDI), zeta potential, and morphological characteristics. Their evaluation was done based on the pharmaceutical, toxicological, and pharmacological parameters. RESULTS AND DISCUSSION: In vitro release of MP + MC from albumin-MP + MC - NPS and MP + MC - NPS was observed to be very controlled for the period of eight days. Cell viability study portrayed non-toxic nature of the developed NPS. Albumin-MP + MC - NPS showed prominent anti-inflammatory potential as compared with non-targeted NPS (MP + MC - NPS) when studied in LPS-induced inflamed astrocytes. Albumin-MP + MC - NPS reduced lesional volume and improved behavioral outcomes significantly in rats with SCI (hemisectioned injury model) when compared with that of MP + MC - NPS. CONCLUSIONS: Albumin-coupled NPS carrier offered an effective method of SCI treatment following safe co-administration of MP and MC. The in vitro and in vivo effectiveness of MP + MC was improved tremendously when compared with the effectiveness showed by MP + MC - NPS. That could be attributed to the site specific, controlled release of MP + MC to the inflammatory site.

MicroRNA-181 inhibits proliferation and promotes apoptosis of chondrocytes in osteoarthritis by targeting PTEN.

OBJECTIVE: To investigate the effects of microRNA-181 (miR-181) on the proliferation and apoptosis of chondrocytes in osteoarthritis (OA) by targeting PTEN. METHODS: The chondrocytes in logarithmic growth phase were selected and divided into 6 test groups: the normal, blank, negative control, miR-181 mimic, miR-181 inhibitor, and miR-181 inhibitor + PTEN-siRNA groups. Reverse transcription qPCR was used to detect the expressions of miR-181 and PTEN mRNA. MTT assay and flow cytometry were performed to detect cell proliferation and apoptosis. The protein expressions of PARP and caspase-3 and the activity of MMP-2 and MMP-9 were detected by Western blotting and gelatin zymography assay. RESULTS: The miR-181 mimic group showed increased miR-181 expression and decreased PTEN expression compared with the other 5 groups. Also, by comparison with the other 5 groups, the cell proliferation rate declined and the rate of cell apoptosis was elevated in the miR-181 mimic group. The MiR-181 mimic group showed remarkably increased protein expression of caspase-3 and PARP compared with the other 5 groups. The activity of MMP-2 and MMP-9 was higher in the miR-181 mimic group than the other 5 groups. CONCLUSION: MiR-181 could up-regulate the expressions of caspase-3, PARP, MMP-2, and MMP-9, and thereby inhibit cell proliferation and promote apoptosis of chondrocytes in OA by targeting PTEN.

Treatment of aseptic diaphyseal nonunion of the lower extremities with exchange intramedullary nailing and blocking screws without open bone graft.

OBJECTIVE: To report the preliminary results of the treatment of aseptic diaphyseal nonunion of the lower extremities with exchange nailing plus blocking screws. METHODS: Between June 2005 and September 2008, twelve patients with diaphyseal nonunion in the lower extremities (femur in five patients and tibia in seven; hypertrophic nonunion in eight patients and atrophic nonunion in four) were treated by reaming, exchanging the original intramedullary nail with a larger one, and using blocking screws, and the therapeutic effect assessed. RESULTS: All patients were followed up for 1-2 years (average, 1.5 years) to assess union. Bony union was achieved in all patients within 4.7-13.5 months (average, 7.8 months). All patients were pain free without any complications by the last follow-up. CONCLUSION: The therapeutic method of exchanging the nail combined with blocking screws is effective for aseptic nonunion of the lower extremity after intramedullary nailing.