Comparison of Clinical and Radiological Outcomes between Calibratable Patient-Specific Instrumentation and Conventional Operation for Medial Open-Wedge High Tibial Osteotomy: A Randomized Controlled Trial.

Background: High tibial osteotomy (HTO) is an effective surgery in treating medial compartment knee osteoarthritis (KOA) combined with varus deformity. An accurate orthopaedy is the key and challenge to the success of HTO. Therefore, we designed a calibratable patient-specific instrumentation (PSI) to assist surgery and evaluated its accuracy and clinical outcomes by comparing with conventional operation (CO). Materials and Methods: 37 patients (39 knees) with medial compartment KOA were randomly divided into the PSI and CO groups and underwent medial open-wedge high tibial osteotomy (MOWHTO) from September 2020 to May 2021. The postoperative radiological outcomes were compared with the preoperative measurements or target values to evaluate the accuracy of correction in the two groups. The American Knee Society Score (AKSS), complication rate, number of intraoperative radiation exposures, blood loss volume, and operative duration were analysed to evaluate the clinical outcomes in the two groups. Results: The designed target values were better achieved in the PSI group than in the CO group. The mean absolute difference between the postoperative measurements and preoperative targets was significantly lower in the PSI group than in the CO group (weight-bearing line (WBL) ratio, 1.97 ± 1.83% vs.5.42 ± 4.41%, P = 0.002; hip-knee-ankle (HKA) angle, 1.12 ± 0.86° vs. 2.27 ± 1.97°, P = 0.018). The operative duration was significantly shorter (P = 0.014), and the number of radiation exposures (P < 0.001) and volume of intraoperative blood loss (P = 0.003) were significantly lower in the PSI group than in the CO group. The clinical AKSS score at 3 and 6 months postoperatively and the functional AKSS score at 3 months postoperatively were significantly higher in the PSI group than in the CO group (P = 0.042, 0.040, and 0.034, respectively). Conclusion: For patients with medial compartment KOA, calibratable PSI can assist the surgeon in MOWHTO with superior accuracy and clinical efficacy. This study was conducted under Randomized Controlled Trial Details (RCT) with Registry Number ChiCTR2000038619.

[Retracted] microRNA­145 inhibits osteosarcoma cell proliferation and invasion by targeting ROCK1.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that several of the data panels shown in Fig. 4A were overlapping with panels contained within the same figure, where the panels were intended to portray the results from a range of different cell migration assay experiments. Given the number of overlaps of data that have been identified, the Editor of Molecular Medicine Reports has decided that this paper should be retracted from the Journal on account of a lack of confidence in the presented data. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a satisfactory reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 10: 155­160, 2014; DOI: 10.3892/mmr.2014.2195].

Single-cell RNA sequencing deconvolutes the in vivo heterogeneity of human bone marrow-derived mesenchymal stem cells.

Bone marrow-derived mesenchymal stem cells (BM-MSCs) are multipotent stromal cells that have a critical role in the maintenance of skeletal tissues such as bone, cartilage, and the fat in bone marrow. In addition to providing microenvironmental support for hematopoietic processes, BM-MSCs can differentiate into various mesodermal lineages including osteoblast/osteocyte, chondrocyte, and adipocyte that are crucial for bone metabolism. While BM-MSCs have high cell-to-cell heterogeneity in gene expression, the cell subtypes that contribute to this heterogeneity in vivo in humans have not been characterized. To investigate the transcriptional diversity of BM-MSCs, we applied single-cell RNA sequencing (scRNA-seq) on freshly isolated CD271+ BM-derived mononuclear cells (BM-MNCs) from two human subjects. We successfully identified LEPRhiCD45low BM-MSCs within the CD271+ BM-MNC population, and further codified the BM-MSCs into distinct subpopulations corresponding to the osteogenic, chondrogenic, and adipogenic differentiation trajectories, as well as terminal-stage quiescent cells. Biological functional annotations of the transcriptomes suggest that osteoblast precursors induce angiogenesis coupled with osteogenesis, and chondrocyte precursors have the potential to differentiate into myocytes. We also discovered transcripts for several clusters of differentiation (CD) markers that were either highly expressed (e.g., CD167b, CD91, CD130 and CD118) or absent (e.g., CD74, CD217, CD148 and CD68) in BM-MSCs, representing potential novel markers for human BM-MSC purification. This study is the first systematic in vivo dissection of human BM-MSCs cell subtypes at the single-cell resolution, revealing an insight into the extent of their cellular heterogeneity and roles in maintaining bone homeostasis.

MicroRNA-133b inhibits the migration and invasion of non small cell lung cancer cells via targeting FSCN1.

[This retracts the article DOI: 10.3892/ol.2016.5044.].

[Retracted] MicroRNA­145 inhibits migration and invasion via inhibition of fascin 1 protein expression in non­small­cell lung cancer cells.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the Transwell cell migration data shown in Fig. 4 were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive any reply. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in Molecular Medicine Reports 12: 6193­6198, 2015; DOI: 10.3892/mmr.2015.4163].

MicroRNA-183 attenuates osteoarthritic pain by inhibiting the TGFα-mediated CCL2/CCR2 signalling axis.

AIMS: MicroRNA-183 (miR-183) is known to play important roles in osteoarthritis (OA) pain. The aims of this study were to explore the specific functions of miR-183 in OA pain and to investigate the underlying mechanisms. METHODS: Clinical samples were collected from patients with OA, and a mouse model of OA pain was constructed by surgically induced destabilization of the medial meniscus (DMM). Reverse transcription quantitative polymerase chain reaction was employed to measure the expression of miR-183, transforming growth factor α (TGFα), C-C motif chemokine ligand 2 (CCL2), proinflammatory cytokines (interleukin (IL)-6, IL-1ß, and tumour necrosis factor-α (TNF-α)), and pain-related factors (transient receptor potential vanilloid subtype-1 (TRPV1), voltage-gated sodium 1.3, 1.7, and 1.8 (Nav1.3, Nav1.7, and Nav1.8)). Expression of miR-183 in the dorsal root ganglia (DRG) of mice was evaluated by in situ hybridization. TGFα, CCL2, and C-C chemokine receptor type 2 (CCR2) levels were examined by immunoblot analysis and interaction between miR-183 and TGFα, determined by luciferase reporter assay. The extent of pain in mice was measured using a behavioural assay, and OA severity assessed by Safranin O and Fast Green staining. Immunofluorescent staining was conducted to examine the infiltration of macrophages in mouse DRG. RESULTS: miR-183 was downregulated in tissue samples from patients and mice with OA. In DMM mice, overexpression of miR-183 inhibited the expression of proinflammatory cytokines (IL-6, IL-1ß, TNF-α) and pain-related factors (TRPV1, Nav1.3, Nav1.7, Nav1.8) in DRG. OA pain was relieved by miR-183-mediated inhibition of macrophage infiltration, and dual luciferase reporter assay demonstrated that miR-183 directly targeted TGFα. CONCLUSION: Our data demonstrate that miR-183 can ameliorate OA pain by inhibiting the TGFα-CCL2/CCR2 signalling axis, providing an excellent therapeutic target for OA treatment. Cite this article: Bone Joint Res 2021;10(8):548-557.

PR11-364P22.2/ATF3 protein interaction mediates IL-1ß-induced catabolic effects in cartilage tissue and chondrocytes.

Osteoarthritis (OA) is a degenerative joint disease which lacks effective medical treatment due to ill-defined molecular mechanisms underlying the pathology. Inflammation is a key factor that induces and aggravates OA. Therefore, the current study aims to explore roles of the dysregulated long non-coding RNAs in the pro-inflammatory cytokine IL-1ß-mediated catabolic effects in cartilage tissue and chondrocytes. We identified RP11-364P22.2 as dysregulated in OA patient-derived cartilage tissues and highly responsive to IL-1ß stimulus. RNA pull-down coupled with mass spectrometry demonstrated that RP11-364P22.2 physically binds to activating transcription factor 3 (ATF3) and thus increases the protein stability and facilitates its nuclear translocation. Loss- and gain-of-function assays indicated that the interaction between RP11-364P22.2 and ATF3 is indispensable for the detrimental effects of IL-1ß including growth inhibition, apoptosis induction as well as degradation of the key chondrocyte structural proteins of type II collage and Aggrecan and synthesis of the extracellular matrix-degrading enzyme MMP13 in chondrocytes. In vivo, depletion of the RP11-364P22.2 effector ATF3 drastically prevented OA development in the rats with surgical destabilization of the medial meniscus (DMM). These results highlight the important roles of lncRNAs in the pathogenesis of OA and indicate the RP11-364P22.2/ATF3 regulatory axis as a potential therapeutic target of inflammation-induced OA.

CREB Ameliorates Osteoarthritis Progression Through Regulating Chondrocytes Autophagy via the miR-373/METTL3/TFEB Axis.

Osteoarthritis (OA) is a degenerative joint disease characterized by articular cartilage degradation. Dysregulated autophagy is a major cause of OA. However, the underlying mechanism is unclear. Here, we found that the expression of element-binding protein (CREB) was downregulated in both cartilage tissues of OA patients and mouse OA model. In tert-butyl hydroperoxide solution-treated chondrocytes, increased apoptosis and autophagic blockage were attenuated by CREB overexpression. Mechanically, MiR-373 directly targeted the 3'UTR of methyltransferase-like 3 (METTL3) and led to its downregulation. METTL3 epigenetically suppressed TFEB. The upregulation of miR-373 by CREB overexpression induced the release of TFEB from METTL3 and restored the autophagy activity of chondrocytes. Taken together, our study showed that CREB alleviates OA injury through regulating the expression of miR-373, which directly targeted METTL3, and finally relieved TFEB from METTL3-mediated epigenetic suppression. The CREB/miR-373/METTL3/TFEB axis may be used as a potential target for the treatment of OA.

Inhibition of microRNA-27b-3p relieves osteoarthritis pain via regulation of KDM4B-dependent DLX5.

Osteoarthritis (OA) represents a progressive degenerative disorder that predominantly affects the synovial membranes of joints. Recent studies have highlighted the significant role played by microRNAs (miRNAs) in OA development. The current study aimed to elucidate the underlying modulatory role of miR-27b-3p in the development of OA. The expression of miR-27b-3p in the OA patients and rat models post anterior cruciate ligament transection operation was measured using reverse transcription quantitative polymerase chain reaction, through which overexpressed miR-27b-3p was found in both of the samples. To further explore the miR-27b-3p functions in OA, western blot analysis, enzyme-linked immunosorbent assay, and ß-galactosidase activity assay were conducted with the results showing that knockdown of miR-27b-3p promoted expression of the osteogenic differentiation markers while inhibiting expression of the adipogenic differentiation markers, inflammatory factors, and cellular senescence of bone marrow mesenchymal stem cells (BMSCs). After that, the interactions between miR-27b-3p, lysine Demethylase 4B (KDM4B), and Distal-Less Homeobox 5 (DLX5) identified using dual-luciferase reporter gene assay and ChIP assay revealed that miR-27b-3p inhibited KDM4B and further reduced expression of DLX5. Finally, the paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were assessed in rat models, and increased PWT and PWL were detected after miR-27b-3p silencing. In conclusion, suppression of miR-27b-3p could enhance KDM4B and DLX5 to alleviate OA pain, shedding light on a new potential therapeutic target for OA.

Application of Self-Made Connection Device in Intractable Intramedullary Device.

BACKGROUND: Intramedullary fixation a standard surgical technique for long bone meta/diaphyseal fractures. There were many difficulties in removal of the intractable intramedullary device. The authors reported a new technique to remove the intractable intramedullary nail by using a self-made connecting device. METHODS: The subject underwent removal of the intramedullary nail using a self-made connecting device, the core components of which were a caudal connecting rod and a sliding hammer in the common intramedullary nail removal device, and the auxiliary device was mainly a clinically commonly used Kirschner wire (K-wire; diameter 1.5-2.5 mm). In technical procedure, the key point was the connection between the k-wire and the intramedullary device, according to the specific conditions of the intramedullary device. RESULTS: From 2012 to 2017, a total of 10 cases of intractable intramedullary devices were taken out using this self-made connection device, including 7 cases of tibial intramedullary nails, 1 case of femoral nail, and 1 case of tibial elastic nail. The technique provided satisfactory results, no infection or re-fracture occurred after the. CONCLUSION: The self-made connecting device may provide new technique for more surgeons in the face of intractable intramedullary device.

Osteoclast-derived miR-23a-5p-containing exosomes inhibit osteogenic differentiation by regulating Runx2.

BACKGROUND: Some microRNAs (miRNAs) are involved in osteogenic differentiation. In recent years, increasing evidences have revealed that exosomes contain specific miRNAs. However, the effect and mechanism of miR-23a-5p-containing exosomes in osteoblast remain largely unclear. METHODS: We extracted exosomes from RANKL-induced RAW 264.7 cells, and identified exosomes via transmission electron microscopy, western blot and flow cytometry analysis. In addition, exosome secretion was inhibited by GW4869 and Rab27a siRNAs. miR-23a-5p expression was analyzed by qRT-PCR, and the related protein levels were examined by western blot assay. Furthermore, the number and distribution of osteoclasts were detected by TRAP staining, and early osteogenesis was evaluated by ALP staining. Combination of YAP1 and Runx2 was verified by Co-IP assay, and the regulation of miR-23a-5p and Runx2 was measured by dual luciferase reporter assay. RESULTS: We successfully extracted exosomes from RANKL-induced RAW 264.7 cells, and successfully verified exosomes morphology. We also indicated that miR-23a-5p was highly expressed in exosomes from RANKL-induced RAW 264.7 cells, and osteoclast-derived miR-23a-5p-containing exosomes inhibited osteoblast activity, while its inhibition weakened osteoclasts. In mechanism, we demonstrated that Runx2 was a target gene of miR-23a-5p, YAP interacted with Runx2, and YAP or Runx2 inhibited MT1DP expression. In addition, we proved that knockdown of MT1DP facilitated osteogenic differentiation by regulating FoxA1 and Runx2. CONCLUSIONS: We demonstrated that osteoclast-derived miR-23a-5p-containing exosomes could efficiently suppress osteogenic differentiation by inhibiting Runx2 and promoting YAP1-mediated MT1DP. Therefore, we suggested miR-23a-5p in exosomes might provide a novel mechanism for osteoblast function.

LncRNA MALAT1 shuttled by bone marrow-derived mesenchymal stem cells-secreted exosomes alleviates osteoporosis through mediating microRNA-34c/SATB2 axis.

Long non-coding RNAs (lncRNAs) have emerged as promising novel modulators during osteogenesis in mesenchymal stem cells (MSCs). Enhanced SATB2 has been demonstrated to promote osteogenic differentiation of bone marrow-derived mesenchymal stem cells (hBMSCs) in patients with osteonecrosis. Preliminary bioinformatic analysis identified putative binding sites between microRNA-34c (miR-34c) and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) or miR-34c and SATB2 3'UTR. Thus, the current study aimed to clarify the potential functional relevance of MALAT1-containing exosomes from BMSCs in osteoporosis. The extracted exosomes from primary BMSCs were co-cultured with human osteoblasts (hFOB1.19), followed by evaluation of the hFOB1.19 cell proliferation, alkaline phosphatase (ALP) activity and mineralized nodules. The obtained findings indicated that BMSC-Exos promoted the expression of SATB2 in osteoblasts, and SATB2 silencing reduced the ALP activity of osteoblasts and mineralized nodules. MALAT1 acted as a sponge of miR-34c to promote the expression of SATB2. Additionally, BMSCs-derived exosomal MALAT1 promoted osteoblast activity. Moreover, in vivo experiments indicated that miR-34c reversed the effect of MALAT1, and SATB2 reversed the effect of miR-34c in ovariectomized mice. Taken together, this study demonstrates that BMSCs-derived exosomal MALAT1 enhances osteoblast activity in osteoporotic mice by mediating the miR-34c/SATB2 axis.

Real-time computerised tomography assisted porous tantalum implant in ARCO stage I-II non-traumatic osteonecrosis of the femoral head: minimum five-year follow up.

PURPOSES: This study was established to investigate the medium-term clinical effect of real-time CT assisted porous tantalum implant for the treatment of ARCO stage I-II non-traumatic osteonecrosis of the femoral head (ONFH). METHODS: This study comprised 24 ONFH patients (29 hips) who were treated with intra-operative real-time CT accurate rapid positioning assisted drilling decompression, lesion removal and porous tantalum implant. Harris score, VAS score and imaging in pre-operation and follow-up period were recorded. RESULTS: The average operative time and intra-operative blood loss were 72.6 min and 158.8 ml, respectively. The mean follow-up was 5.4 years. No femoral head penetrating, wound infection, and death occurred. Harris and VAS score improved significantly (73.78 vs. 88.11; 7.13 vs. 2.66) at last follow-up (P < 0.05). The functional improvement and pain relief rate was 100% at six months after operation. The effective rate was 86.21% at 12 months after operation and last follow-up. Five pre-operative ARCO stage I hips had no radiographic progress. Meanwhile, four among the 24 ARCO stage II hips progressed into stage III between eight and 12 months after surgery, among which two progressed into stage IV and two remained in stage III at the last follow-up. The average value of Kerboul combined necrotic angle was 263.24°. There was no progress in Kerboul combined necrotic angle among the grades 2 and 3 patients. However, among the six cases at grade 4, four cases with post-operative progress, two patients converted to THA. CONCLUSIONS: Our technique is safety and effective in the treatment of ARCO stage I-II non-traumatic ONFH.

MALAT1 enhanced the proliferation of human osteoblasts treated with ultra­high molecular weight polyethylene by targeting VEGF via miR­22­5p.

Osteolysis associated with an implanted prosthesis is the major cause of failure in prosthesis implantation, and a severe public health issue worldwide. The type of bone metabolism associated with this disorder has been a major focus for improving the outcomes of patients with osteolysis. The role of metastasis­associated lung adenocarcinoma transcript 1 (MALAT1; a member of the long coding RNA family) during the onset of osteolysis and the related molecular regulatory mechanism in ultra­high molecular weight polyethylene (UHMWPE)­treated hFOB 1.19 cells were investigated in the current study. The effect of MALAT1 knockdown on cell viability, cell apoptosis and osteolysis­associated signaling were also examined, and the interactions that occurred between MALAT1 and an anti­osteolysis molecule, microRNA (miR)­22­5p were investigated. Additionally, knockdown of vascular endothelial growth factor (VEGF) exerted similar biological effects as observed following miR­22­5p overexpression. The data showed that MALAT1 and pro­osteolysis indicators, receptor activator of nuclear factor­κB ligand (RANKL) and VEGF were upregulated in clinical interface membrane samples. Knockdown of MALAT1 inhibited the growth of UHMWPE­treated hFOB 1.19 cells, and this effect was associated with the upregulation of OPG, and downregulation of RANKL and VEGF. Results of a dual luciferase assay confirmed the interaction between VEGF and miR­22­5p, and also between MALAT1 and miR­22­5p. Additionally, subsequent assays indicated that overexpression of MALAT1 suppressed the anti­osteolysis effect of miR­22­5p, which would further induce VEGF expression. The data indicated that MALAT1 has an in port ant role in the onset of osteolysis via its ability to induce RANKL expression and inhibit the effect of miR­22­5p.

MicroRNA-133b inhibits the migration and invasion of non small cell lung cancer cells via targeting FSCN1.

MicroRNA (miR)-133b has been reported to act as a tumor suppressor in multiple types of human cancers, including non small cell lung cancer (NSCLC). However, the underlying mechanism by which miR-133b inhibits NSCLC metastasis remains largely unclear. In the present study, reverse transcription-quantitative polymerase chain reaction and western blotting were used to detect messenger RNA and protein expression. A wound healing assay and transwell assay were used to examine the cell migration and invasion. The expression level of miR-133b was found to be significantly downregulated in NSCLC cell lines compared with normal lung epithelial BEAS-2B cells. Further investigation identified fascin1 (FSCN1) as a direct target of miR-133b in NSCLC cells. The expression of FSCN1 was significantly increased in NSCLC cell lines compared with BEAS-2B cells, and its protein expression was negatively regulated by miR-133b in NSCLC A549 cells. Further investigation showed that the upregulation of miR-133b notably inhibited NSCLC cell migration and invasion, while the overexpression of FSCN1 significantly promoted NSCLC cell migration and invasion. Furthermore, the overexpression of FSCN1 reversed the suppressive effect of miR-133b overexpression on NSCLC cell migration and invasion. Accordingly, the present study suggests that miR-133b inhibits the migration and invasion of NSCLC cells via directly targeting FSCN1, and thus may be used for the treatment of NSCLC metastasis.

Network Meta-Analysis of Pharmacological Agents for Osteoporosis Treatment and Fracture Prevention.

BACKGROUND AND OBJECTIVE: Osteoporosis afflicts a large number of populations in the world and is featured by systemic impairment of bone mass and strength which may further trigger an increase in the risk of fragile fractures. This network meta-analysis (NMA) is designed to distinguish therapies more preferable than others with respect to efficacy and safety. METHODS: We searched the medical literature for relevant studies systematically. Both direct and indirect evidence were synthesized to compare the efficacy, described by odds ratios (OR) and 95% credible intervals (CrI). Moreover, the surface under cumulative ranking curve was calculated to rank probabilities with respect to clinical outcomes. The new non-vertebral fractures, hip and wrist fractures, and adverse events were evaluated in this NMA. RESULTS: Patients treated by alendronate, denosumab, teriparatide were associated with a reduced risk of new non-vertebral fractures compared to those treated by placebo. Alendronate, denosumab and zoledronic acid had better efficacy in preventing hip fractures. With respect to wrist fractures prevention, no significant difference was observed. Zoledronic acid exhibited significantly increased risk of adverse events than placebo, alendronate, denosumab, and raloxifene. According to SUCRA, teriparatide ranked highest in new non-vertebral fractures prevention, etidronate and denosumab balanced safety and efficacy well. CONCLUSION: In summary, teriparatide appeared to be the most efficacious drug for preventing new non-vertebral fractures, while etidronate and denosumab were preferable for balancing safety and efficacy well.

[A COMPARATIVE STUDY ON TWO OSTEOTOMIES IN TOTAL HIP ARTHROPLASTY FOR CROWE TYPE IV DEVELOPMENTAL DYSPLASIA OF THE HIP].

OBJECTIVE: To assess the effectiveness of two osteotomy methods in total hip arthroplasty (THA) for treating Crowe type IV adult developmental dysplasia of the hip (DDH), trochanteric osteotomy and subtrochanteric osteotomy. METHODS: A retrospective analysis was made on the clinical data of 36 patients (43 hips) with Crowe type IV DDH undergoing THA between June 2007 and December 2013. In THA, 19 patients (23 hips) underwent trochanteric osteotomy (group A) and 17 patients (20 hips) underwent subtrochanteric osteotomy (group B). There was no significant difference in age, gender, body mass index, side, preoperative Harris score, and limb length difference between 2 groups (P>0.05). The operation duration, bleeding volume, hospitalization duration, intraoperative and postoperative complications were compared between 2 groups. RESULTS: There was no significant difference in operation duration, bleeding volume, and hospitalization days between 2 groups (P>0.05). The rate of intraoperative complication was 21.7% (5/23) in group A and 5.0% (1/20) in group B, showing no significant difference between 2 groups (P>0.05). The rate of postoperative complications was 10.5% (2/19) in group A and 22.2% (4/18) in group B, showing no significant difference between 2 groups (P>0.05). Thirty-one patients (37 hips) were followed up 1-7 years (mean, 3 years), including 16 cases (19 hips) in group A and 15 cases (18 hips) in group B. X-ray films showed good position of the prostheses. The Harris score at last follow-up was significantly increased when compared with preoperative score in 2 groups (P<0.05), but there was no significant difference between 2 groups (P>0.05). The postoperative discrepancy of bilateral lower limbs had no significant difference (t = -1.343, P=0.188). CONCLUSION: THA with trochanteric osteotomy or subtrochanteric osteotomy both can effectively treat Crowe type IV DDH. THA with subtrochanteric osteotomy has an advantage in correcting lower limb discrepancy.

MicroRNA-145 inhibits migration and invasion via inhibition of fascin 1 protein expression in non-small-cell lung cancer cells.

MicroRNA (miR)-145 has been shown to act as a suppressor in numerous cancer types, including non-small-cell lung cancer (NSCLC). Fascin 1 (FSCN1), an actin bundling protein, has been implicated in NSCLC. However, the detailed role of miR-145 as well as the association between miR-145 and FSCN1 in the regulation of migration and invasion in NSCLC cells has remained elusive. The present study revealed that miR-145 was downregulated and FSCN1 was upregulated in NSCLC tissues and cell lines. Further investigation showed that overexpression of miR-145 markedly inhibited the protein expression of FSCN1, while knockdown of miR-145 upregulated the protein (but not mRNA) levels of FSCN1 in the NSCLC cell line H129. Moreover, a luciferase reporter assay indicated that FSCN1 is a direct target of miR-145 in NSCLC H129 cells. Furthermore, overexpression of miR-145 markedly inhibited the migration and invasion of NSCLC cells, similar to the effect of small interfering RNA-mediated FSCN1 inhibition in H129 cells. In addition, the inhibitory effect of miR-145 overexpression on migration and invasion was reversed by FSCN1 upregulation in H129 cells. These findings suggested that miR-145 has an inhibitory effect on the migration and invasion in NSCLC cells, at least in part through suppressing the protein expression of its target FSCN1. Therefore, miR-145/FSCN1 may be used as a potential target for the treatment of NSCLC.

microRNA-145 inhibits osteosarcoma cell proliferation and invasion by targeting ROCK1.

Osteosarcoma (OS), a malignant mesenchymal sarcoma, is the most frequent primary bone tumor, with a peak incidence in young children and adolescents. The downregulation of microRNA­145 (miRNA/miR­145) has previously been identified to be associated with the aggressiveness and metastasis of OS. However, the detailed regulatory mechanism by which miR­145 inhibits OS remains largely unknown. The present study demonstrated that miR­145 was significantly downregulated in OS tissues and KHOS and U2OS cell lines. Rho­associated protein kinase 1 (ROCK1), a key regulator of actin cytoskeleton reorganization, was identified as a novel target of miR­145. Ectopic expression of miR­145 notably suppressed the protein expression of ROCK1 without affecting its mRNA level. Furthermore, the expression of ROCK1 was significantly increased in the OS tissues and in the KHOS and U2OS cells. It was further demonstrated that the overexpression of miR­145 downregulated KHOS and U2OS cell proliferation and invasion, which was reversed by restoration of ROCK1. To the best of our knowledge, the present study demonstrates for the first time that, as a tumor suppressor, miRNA­145 inhibits OS cell proliferation and invasion, at least in part by directly targeting ROCK1. These results indicate that miR­145 may be a potential candidate for the diagnosis and treatment of OS.

Greater trochanter osteotomy with cementless THA for Crowe type IV DDH.

This study explored the surgical method and short-term clinical effect of a greater trochanter osteotomy along with cementless artificial total hip arthroplasty in the treatment of Crowe type IV developmental dysplasia of the hip. The authors conducted a retrospective analysis of 18 patients (22 hips) with Crowe type IV dysplasia who were seen between June 2008 and August 2010. After undergoing cementless artificial total hip arthroplasty using a posterolateral approach, a greater trochanter osteotomy was used to adjust the tension of the gluteal muscle, and an acetabular cup was placed. Average preoperative length shortening of the affected limb was 4.5 cm (range, 3.4-6 cm), and average postoperative length increase was 4.0 cm (range, 3.2-4.8 cm). Average postoperative Harris Hip Score was 87 (range, 79-91), which was higher than the average preoperative score of 38 (range, 32-51). Intraoperatively, 3 hips (3 patients) sustained a proximal femur fracture. Due to the stability of the femoral prosthesis, either no treatment or wire fixation only was given; by 2 months postoperatively, radiographs indicated that all fractures had healed. One patient had symptoms of sciatic nerve paralysis that resolved 3 months postoperatively. Performing a greater trochanter osteotomy after cementless artificial total hip arthroplasty is effective for the treatment of Crowe type IV dysplasia and can rebuild the complex biology and biomechanics of hip dysplasia without increasing the complication risk.