microRNA-935-modified bone marrow mesenchymal stem cells-derived exosomes enhance osteoblast proliferation and differentiation in osteoporotic rats.

AIMS: The involvement of several microRNAs (miRNAs) in osteogenic differentiation has been indicated recently. Also, exosomes, derived from different cells, could shuttle specific miRNAs to other cell systems. Nevertheless, the effect and mechanism of microRNA-935 (miR-935)-containing exosomes in osteoblasts remain basically unclear. The current work was set to inspect the relevance of bone marrow mesenchymal stem cells (BMSCs)-derived exosomes (BMSC-exo) carrying miR-935 to osteoporotic rats. METHODS: The extracted BMSCs and purchased osteoblasts were cultured, followed by exosome isolation and identification. After cell grouping, osteoblasts were co-cultured with BMSCs. CCK-8, alizarin red staining as well as ALP staining were performed to detect osteoblast proliferation and activity. The binding connection between miR-935 and signal transducer and activator of transcription 1 (STAT1) was measured by dual-luciferase reporter gene assays. The expression profiles of miR-935, STAT1 and osteoblast-related proteins were assessed by RT-qPCR and Western blot. A rat model with osteoporosis was induced, and the BMD, BV/TV, Tb.N, Tb.Th and Tb.Sp values in rat bone tissues were observed by Micro-CT. RESULTS: BMSC-exo inhibited STAT1 levels by the delivery of miR-935 into osteoblasts, while STAT1 silencing promoted ALP activity in osteoblasts and mineralized nodules. STAT1 was identified as a target gene of miR-935. Moreover, in vivo experiments showed that in ovariectomized rats, silencing of miR-935 significantly reduced BMD, BV/TV, Tb.N, Tb.Th and increased Tb.Sp. CONCLUSION: BMSC-exo carry miR-935 to promote osteoblast proliferation and differentiation through targeting STAT1.

CircRNA_25487 inhibits bone repair in trauma-induced osteonecrosis of femoral head by sponging miR-134-3p through p21.

We aimed to identify specific circular RNAs (circRNAs) involved in bone repair of trauma-induced osteonecrosis of femoral head (TIONFH) and to explore the potential mechanism. CircRNA sequencing on the blood sample collected from patients with and without TIONFH was performed to select cirRNAs that were significantly differentially expressed, followed by qRT-PCR confirmation. Furthermore, the functions of one selected circRNA and the potential mechanisms in bone repair of TIONFH were validated based on the bone marrow mesenchymal stem cells (BMSCs) and osteoclast-like cells (OLCs) through CCK-8, flow cytometry, transwell assay, luciferase reporter assay, and western blot. A total of 234 upregulated and 148 downregulated differentially expressed circRNAs were identified, and qRT-PCR showed that circRNA_25487 was significantly upregulated in the peripheral blood of TIONFH patients. Luciferase reporter assay confirmed the binding effect between miR-134-3p and circRNA_25487. CircRNA_25487 suppression and miR-134-3p overexpression could promote cell proliferation and invasion while inhibited apoptosis of BMSCs and OLCs. miR-134-3p could target p21. CircRNA_25487 inhibited bone repair in TIONFH by sponging miR-134-3p to upregulate the expression of p21.

LncRNA NKILA integrates RXFP1/AKT and NF-κB signalling to regulate osteogenesis of mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are previously found to have potential capacity to differentiate into osteocytes when exposed to specific stimuli. However, the detailed molecular mechanism during this progress remains largely unknown. In the current study, we characterized the lncRNA NKILA as a crucial positive regulator for osteogenesis of MSCs. NKILA attenuation significantly inhibits the calcium deposition and alkaline phosphatase activity of MSCs. More interestingly, we defined that NKILA is functionally involved in the regulation of RXFP1/PI3K-AKT and NF-κB signalling. Knockdown of NKILA dramatically down-regulates the expression of RXFP1 and then reduces the activity of AKT, a downstream regulator of RXFP1 signalling which is widely accepted as an activator of osteogenesis. Moreover, we identify NF-κB as another critical regulator implicated in NKILA-mediated osteogenic differentiation. Inhibition of NF-κB can induce the expression of RUNX2, a master transcription factor of osteogenesis, in a HDAC2-mediated deacetylation manner. Thus, this study illustrates the regulatory function of NKILA in osteogenesis through distinct signalling pathways, therefore providing a new insight into searching for new molecular targets for bone tissue repair and regeneration.

Analysis of damage in relation to different classifications of pre-collapse osteonecrosis of the femoral head.

Objective This study aimed to investigate the damage pattern of the stress transfer path (STP) for the Japanese Investigation Committee (JIC) classification of pre-collapse osteonecrosis of the femoral head. We aimed to provide a specific biomechanical basis for treatment decisions of each subtype. Methods Five computational models were used in the experiment. Different necrotic classifications were simulated based on the JIC classification system. Damage patterns of the STP were used for qualitative assessment and average stresses were used for quantitative analysis. Results The STP of type A showed a strong similarity to the healthy level, which was consistent with the bone density distribution in X-rays and previous simulations results. The damaged area of principal stress of type B was approximately 25% of the healthy level. The STPs of types C1 and C2 were broken and the damaged areas of principal stress were more than 50% of the healthy level. The efficiency of stress transfer was reduced. Conclusions These results indicate that the damage patterns and stress transfer efficiency of the femoral head are associated with necrotic classifications.

Multiple cannulated screws vs. dynamic hip screws for femoral neck fractures : A meta-analysis.

OBJECTIVE: Various fixation devices have been reported for stabilization of femoral neck fractures. Numerous studies on arthroplasty versus internal fixation devices in the treatment of femoral neck fractures have been performed, but the optimal approach for internal fixation has not been analyzed. METHODS: A meta-analysis and system evaluation were performed to compare clinical effects. We searched PubMed, Embase, Cochrane Library, and Web of ScienceTM for randomized, controlled trials (RCTs) comparing multiple cannulated screws (MCS) with dynamic hip screws (DHS) and analyzed the failure rate of operations, the reoperation rate, and postoperative complications. Risk ratios (RRs) and mean differences from each trial were pooled using random effects or fixed effects models, depending on study heterogeneity. The analysis was performed using RevMan5.2. RESULTS: In this meta-analysis, 592 femoral neck fractures from 7 studies were assessed, and the meta-analysis results indicated significant differences in reoperation (RR 1.44, 95% confidence interval [CI] 1.10-1.88, P = 0.008) and failure rate (RR 2.28, 95% CI 1.10-4.72, P = 0.03), but no significant differences in the rate of postoperative complications between the MCS group and DHS group. CONCLUSIONS: DHS fixation has a larger skin incision and more soft tissue dissection, but it is associated with lower rates of fixation failure, reoperation, and overall rate of postoperative complications, and its use in elderly patients with osteoporosis is still recommended due to simplicity, efficacy, and high overall success rate. Multicenter RCTs with large samples are needed to better understand the comparative efficacy and safety of MCS and DHS in femoral neck fractures of restricted fracture type.

What is the optimal approach for tranexamic acid application in patients with unilateral total hip arthroplasty?

PURPOSE: In the total hip arthroplasty (THA), the optimal administration route of tranexamic acid (TXA) remains controversial. This study was designed to investigate the impact of topical injection of TXA on blood loss during primary unilateral THA as well as short-term safety and adverse side effects compared with intravenous administration of TXA. MATERIAL AND METHODS: In this study, 75 patients who underwent unilateral THA were randomly divided into 3 groups receiving intra-articular TXA (IA group), intravenous TXA (IV group) or no TXA (control group C). Blood loss, postoperative drainage, covert blood loss, total blood volume, the number of blood transfusions after surgery and transfusion rate, incidence of deep venous thrombosis and pulmonary embolism were recorded and evaluated in the three groups after 1 week and 1 month. RESULTS: There were significant differences in the quantity of postoperative drainage, covert blood loss, total blood volume, the number of blood transfusions after surgery and transfusion rates between the three groups (P < 0.05), but blood loss during surgery showed no significant differences among the three groups (P > 0.05). In the IV group, 1 patient suffered from deep venous thrombosis of the lower limbs and in the C group, 2 patients suffered from superficial venous thrombosis of the lower limbs 2 and 4 days after surgery, respectively. In the IA group no complications occurred during the follow-up period. CONCLUSION: Preoperative intravenous TXA and postoperative topical TXA significantly reduced postoperative blood loss and transfusion rates among the patients who underwent primary unilateral THA and the short-term safety was good. The data suggest that topical injection of TXA is safer and more effective, without postoperative complications.