Jingsheng Shi

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.

Three-dimensional virtual reality simulation of periarticular tumors using Dextroscope reconstruction and simulated surgery: a preliminary 10-case study.

BACKGROUND Dextroscope® three-dimensional (3D) imaging has been extensively used to generate virtual reality (VR) workspaces for neurosurgery and laparoscopy, but few applications have been reported for orthopedic surgery. Here, we investigated orthopedic periarticular tumor surgery planning and anatomical characteristics using a Dextroscope. MATERIAL AND METHODS Patients undergoing surgery for periarticular tumors (n=10) between October 2008 and June 2010 were enrolled and presurgically subjected to computed tomography (CT), magnetic resonance imaging (MRI), and MRI angiography (MRI-A). Imaging data were transferred and integrated in a Dextroscope to produce a VR simulation. The presurgical 3D anatomical reconstructions and intraoperative anatomical characteristics (virtual vs. actual data) and surgical approach (virtual vs. actual situation) measurement and subjective appearance were compared. RESULTS Anatomical characteristics in the area of interest and tumor diameters in all 3 planes (superior-inferior, medial-lateral, and anteroposterior) were consistent between virtual and actual data (3.92±1.22, 1.96±0.53, and 1.73±0.44 vs. 3.92±1.13, 1.91±0.44, and 1.81±0.41; P=0.99, 0.24, and 0.09, respectively). However, the virtual surgical situations were inconsistent with the actual intraoperative situation in many cases, leading to complications. The resolutions of the original CT, MRI, and MRI-A images directly correlated with 3D simulation quality, with soft tissues most poorly represented. Tumor tissue imaging quality in 3D varied extensively by tumor type. CONCLUSIONS Anatomical structures of periarticular tumors can be reconstructed using the Dextroscope system with good accuracy in the case of simple fenestration, increasing treatment individualization, surgical competence level, and potentially reducing intraoperative complications. However, further specialization of VR tools for use in orthopedic applications that involve specialized tools and procedures, such as drilling and implant placement, are urgently need.

Total knee arthroplasty using trochlear groove as guide for position of femoral component in severe knee osteoarthritis

BackgroundApart from transepicondylar axis, the native femoral sulcus was also reported to be used as a guide for the femoral component position in total knee arthroplasty (TKA). However, it was not shown in patients with severe knee osteoarthritis. This study was conducted to compare the position of trochlear groove in patients with and without osteoarthritis, and to assess whether trochlear groove could be used as a guide for position of femoral component in TKA for severe knee osteoarthritis.MethodsTotal 50 severe knee osteoarthritis patients (Kellgren Lawrence grade 3 or 4) who underwent TKA were included. Meanwhile, 50 patients who underwent arthroscopic surgery without osteoarthritis were included as control. The distance from trochlear groove to the midpoint of a virtual anterior condyle osteotomy line (parallel to the posterior condyle line) (a–b) was recorded by radiological and surgical measurements. Midpoint of transepicondylar axis and trochlear groove were used as guide for placing prosthesis model in TKA, respectively. No-thumb test was performed to assess the patellar tracking. The position of femoral component was finally performed using trochlear groove as guide in TKA.ResultsValue of “a–b” was significantly different between osteoarthritic and control knees (P = 0.008). During the placement of prosthesis model, similar patellar tracking was detected between using midpoint of transepicondylar axis and trochlear groove as guide (P > 0.05). After placing femoral component using trochlear groove as guide, most patients obtained good patellofemoral congruence with pneumatic tourniquet inflated (n = 43) or deflated (n = 5), and good patellofemoral congruence was also obtained by lateral patellar retinaculum release in two patients.ConclusionDespite the shifting of trochlear groove caused by severe knee osteoarthritis, trochlear groove can be used as a guide for position of femoral component, with equivalent patellar tracking compared with transepicondylar axis.

Evaluation of the 3D finite element method using a tantalum rod for osteonecrosis of the femoral head.

Background The aim of this study was to contrast the collapse values of the postoperative weight-bearing areas of different tantalum rod implant positions, fibula implantation, and core decompression model and to investigate the advantages and disadvantages of tantalum rod implantation in different ranges of osteonecrosis in comparison with other methods. Material/Methods The 3D finite element method was used to establish the 3D finite element model of normal upper femur, 3D finite element model after tantalum rod implantation into different positions of the upper femur in different osteonecrosis ranges, and other 3D finite element models for simulating fibula implant and core decompression. Results The collapse values in the weight-bearing area of the femoral head of the tantalum rod implant model inside the osteonecrosis area, implant model in the middle of the osteonecrosis area, fibula implant model, and shortening implant model exhibited no statistically significant differences (p>0.05) when the osteonecrosis range was small (60°). The stress values on the artificial bone surface for the tantalum rod implant model inside the osteonecrosis area and the shortening implant model exhibited statistical significance (p<0.01). Conclusions Tantalum rod implantation into the osteonecrosis area can reduce the collapse values in the weight-bearing area when osteonecrosis of the femoral head (ONFH) was in a certain range, thereby obtaining better clinical effects. When ONFH was in a large range (120°), the tantalum rod implantation inside the osteonecrosis area, shortening implant or fibula implant can reduce the collapse values of the femoral head, as assessed by other methods.

Use of extended curettage with osteotomy and fenestration followed by reconstruction with conservation of muscle insertion in the treatment of Enneking stage II locally aggressive bone tumor of the proximal extremities: resection and treatment of bone tumors

BackgroundThe purpose of this study was to investigate the clinical efficacy of extended resection with osteotomy, fenestration and conservation of muscle (tendon) insertion in the treatment of bone tumors.MethodsA total of 15 patients with locally aggressive bone tumors (Enneking stage II) in the adjacent muscle (tendon) insertion of the proximal extremity were enrolled in the present study (mean age of 29 years). Extended curettage of lesions with osteotomy, fenestration and/or conservation of muscle (tendon) insertion and internal fixation with a bone graft or bone cement was performed at stage I. Postsurgical brace protection was used for 4 to 12 weeks and the patients were periodically followed-up by X-ray and functional assessment. Recurrence, postsurgical Enneking score and outcome rating were assessed.ResultsTreated cases included 15 patients aged 29 ±7.75 years (range, 18 to 42) with a male to female ratio of 8:7. Six had a femoral tumor and nine had a humeral tumor. These tumors comprised three chondroblastomas, five giant-cell tumors and seven aneurysmal bone cysts. Follow-up for 48 ±12.95 months (range, 25 to 72) revealed that 13 of 15 (87%) patients exhibited no recurrence. Local recurrence was observed in a patient with an aneurysmal bone cyst (nine months) and one with a giant-cell tumor (12 months). Mean Enneking scores were 27 ±4.07 (range, 18 to 29). Except for the patient with the recurrent giant-cell tumor, all patients reported good (13%, 2 out of 15) or very good (80%, 12 out of 15) outcomes. Very good outcomes were reported in 92% of patients (12 out of 13) without recurrence.ConclusionsThe procedures used in this study achieved high clinical efficacy, complete lesion removal, reduced recurrence and good restoration of joint function in patients with primary locally aggressive Enneking stage II bone tumors of the proximal extremities.

Radius neck-to-humerus trochlea transposition elbow reconstruction after proximal ulnar metastatic tumor resection: case and literature review.

Wide en bloc excision of proximal ulna sections is used to treat traumatic and pathological fractures of the ulna, though poor standardization of clinical treatment often results in long-term failure of such reconstructed biomechanical structures. In order to provide insight into effective ulnar reconstructive treatments, the case of an 80-year-old Chinese Han male presenting with pathological fracture caused by a proximal ulnar metastatic tumor concurrent with metastatic renal cancer complicated by occurrence in the brain and lungs is reported and contrasted with alternative treatment techniques. Wide resectioning of the proximal ulna and reconstruction with local radius neck-to-humerus trochlea transposition resulted in preservation of functionality, sensitivity, and biomechanical integrity after postsurgical immobilization, 6 weeks of passive- and active-assisted flexion, and extension with a hinged brace. The resultant Musculoskeletal Tumor Society rating score was 25 of 30 (83 %). Full sensitivity and mobility of the left hand and elbow (10° to 90° with minimally impaired supination and pronation) was restored with minimal discomfort. No evidence of local recurrence or other pathological complications were observed within a 1-year follow-up period. Efficient reconstruction of osseous and capsuloligamentous structures in the elbow is often accomplished by allografts, prosthesis, and soft tissue reconstruction, though wide variations in risk and prognosis associated with these techniques has resulted in disagreements regarding the most effective standards for clinical treatment. Current findings suggest that radius neck-to-humerus trochlea transposition offers a superior range of elbow movement and fewer complications than similar allograft and prosthetic techniques for patients with multiple metastatic cancers.

FGF2 and FAM201A affect the development of osteonecrosis of the femoral head after femoral neck fracture

Osteonecrosis of the femoral head (ONFH) is a common orthopedic disease associated with high disability, and femoral neck fracture (FNF) is one of the most common reasons for traumatic ONFH. This study was designed to reveal the mechanisms underlying ONFH. Using fastx_toolkit and prinseq-lite tools, quality control was conducted for the sequencing data. The differentially expressed genes (DEGs, including both mRNAs and lncRNAs) between ONFH and FNF samples were identified using the edgeR package in R, and were then subjected to enrichment analysis using the BioCloud platform. Subsequently, protein-protein interaction (PPI) networks were constructed using Cytoscape software. After the target genes of DE-lncRNAs were predicted based on Spearmans rank correlation coefficient, lncRNA-gene coexpression network was visualized using the Cytoscape software. Furthermore, functional enrichment analysis was carried out for the target genes using the clusterprofiler package in R. Additionally, the key genes were detected by quantitative real-time polymerase chain reaction (qRT-PCR). A total of 2965 DEGs were identified from the ONFH samples, including 602 DE-lncRNAs (such as downregulated FAM201A). In the PPI networks, eight upregulated genes (including FGF2, IGF1, SOX9, and COL2A1) and 11 downregulated genes were among the top 20 genes according to all of the scores, such as degree centrality, closeness centrality, and betweenness centrality scores. Functional enrichment analysis showed that IGF1, SOX9, and COL2A1 were significantly enriched during skeletal system development. Moreover, qRT-PCR experiments detected the upregulation of FGF2 and downregulation of FAM201A in ONFH samples. FGF2 and FAM201A were correlated with the development of ONFH. Besides, IGF1, SOX9, and COL2A1 might also affect the pathogenesis of ONFH.

Norcantharidin modulates the miR-30a/Metadherin/AKT signaling axis to suppress proliferation and metastasis of stromal tumor cells in giant cell tumor of bone

Giant cell tumor of bone (GCTB) is a benign but locally aggressive tumor, which can cause significant bone destruction at the epiphysis of long bones. Recent studies have demonstrated that norcantharidin (NCTD) can inhibit the proliferation and migration of various human cancer cells, but the role of NCTD in GCTB has not previously been evaluated. The aim of this study was to explore the nature of the anti-cancer effects of NCTD in GCTB and to elucidate the biomolecular mechanisms responsible for these effects. Primary stromal cell cultures, representing the main neoplastic component of GCTB, were used for cell-based experiments. Firstly, the anti-cancer effects of NCTD on GCTB stromal tumor cells were investigated by CCK-8 assay, flow cytometry and transwell invasion assay. Next, microRNA (miRNA) microarray and quantitative reverse transcription PCR (qRT-PCR) analyses were performed to examine and verify altered expression of miRNAs associated with NCTD treatment. Subsequently, the GCTB stromal cells were transfected with miR-30a inhibitor to confirm its involvement in the observed anti-cancer effects of NCTD. Luciferase reporter assays were carried out to identify the target gene of miR-30a. Moreover, changes in the expression of protein markers of AKT signaling were measured by Western Blot analysis. The results demonstrated that NCTD treatment could inhibit cell proliferation, block the cell cycle process and induce cell apoptosis in GCTB stromal cells. An inhibitory effect of NCTD on GCTB stromal cell invasion through inhibition of epithelial mesenchymal transition (EMT) was also observed. Expression of miR-30a was significantly upregulated by NCTD treatment and miR-30a knockdown significantly reversed the anti-tumor effects of NCTD against GCTB stromal cells. Of note, metadherin (MTDH), a novel oncogene which modulates the AKT pathway, was identified as a direct target of miR-30a in GCTB stromal cells. Further data showed that miR-30a could negatively regulate the expression of MTDH and the AKT pathway in GCTB stromal cells. Importantly, MTDH expression was found to be inversely correlated with miR-30a expression in clinical GCTB specimens. Moreover, NCTD treatment effectively suppressed the AKT signaling pathway as demonstrated by downregulation of phosphorylated-Akt S473 (p-Akt S473), p-Akt (T308), phosphorylated-glycogen synthase kinase (GSK)3β (p-GSK3β) and c-Myc, whilst miR-30a inhibition re-activated the AKT signaling pathway in GCTB stromal cells. Our findings demonstrate that NCTD can inhibit cell proliferation and metastasis of GCTB stromal cells in vitro, via modulating the miR-30a/MTDH/AKT signaling axis. This suggests that NCTD has potential as a novel therapeutic treatment for GCTB.