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Qing Liu,1– 3 Hongbo He,1 Zhixi Duan,1,4 Hao Zeng,1 Yuhao Yuan,1 Zhiwei Wang,1 Wei Luo1 1Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 2Department of Spine Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 3Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, USA; 4Department of Orthopedics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Wei LuoDepartment of Orthopaedics, Xiangya Hospital, Central South University, Changsha 410008, People’s Republic of ChinaTel +86 15116329088Email luowei0928@126.comAim: To evaluate the clinical effect of intercalary allograft transplantation and reconstruction in the treatment of diaphyseal defect after resection of lower extremity malignant bone tumor.Methods: Clinical data of 17 patients diagnosed with malignant lower-limb bone tumors and having undergone segmental allograft reconstruction with a mean follow-up of 49.8 (26– 78) months were included. Segmental allografts of average 17-cm length preserved by deep-freezing were used and fixed using intramedullary nail, double plate, and intramedullary nail and plate combination in 2, 5, and 10 patients, respectively. Host–donor junctions were perfectly and roughly matched in 5 and 12 patients, respectively. Allograft union, local recurrence, and complications were assessed using clinical and radiological tests. Allograft union was evaluated using the International Society of Limb Salvage (ISOLS) scoring system. The functional prognosis was evaluated using the Musculoskeletal Tumour Society (MSTS) scoring system.Results: Intercalary allograft reconstruction of femoral shaft, tibial shaft, and distal tibia with ankle arthrodesis was performed in eight, four, and five patients, respectively. Two patients had local recurrence and underwent amputation; one died of metastasis. Host–donor junctions in two patients showed nonunion; 12 patients achieved bone union. The average union time was 12.1 months. No allograft fracture or infection occurred. Union rates were 100% and 88.2% at metaphyseal and diaphyseal junctions, respectively. Healing time differed significantly between the precisely and roughly matched groups (p< 0.01). The incidence of nonunion was higher after intramedullary nailing than after the other two methods (p< 0.05). The mean MSTS score was 24.2 (14– 29) at the end of follow-up.Conclusion: Intercalary allograft transplantation is an effective strategy for diaphyseal defect following post-tumor resection in the lower extremity. Good bone healing after allograft reconstruction is achieved with stable internal fixation and perfectly matched host–donor interfaces.Keywords: intercalary allograft, malignant bone tumor, bone healing, lower extremity, internal fixation

Background Osteoarthritis (OA) is the most common chronic joint disease worldwide. It is characterized by pain and limited mobility in the affected joints and may even cause disability. Effective clinical options for its prevention and treatment are still unavailable. This study aimed to identify differences in gene signatures between tissue samples from OA and normal knee joints and to explore potential gene targets for OA. Methods Five gene datasets, namely GSE55457, GSE55235, GSE12021, GSE10575, and GSE1919, were selected from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified using the R programming software. The functions of these DEGs were analyzed, and a protein–protein interaction (PPI) network was constructed. Subsequently, the most relevant biomarker genes were screened using a receiver operating characteristic (ROC) curve analysis. Finally, the expression of the protein encoded by the core gene PTHLH was evaluated in clinical samples. Results Eleven upregulated and 9 downregulated DEGs were shared between the five gene expression datasets. Based on the PPI network and the ROC curves of upregulated genes, PTHLH was identified as the most relevant gene for OA and was selected for further validation. Immunohistochemistry confirmed significantly higher PTHLH expression in OA tissues than in normal tissues. Moreover, similar PTHLH levels were detected in the plasma and knee synovial fluid of OA patients. Conclusion The bioinformatics analysis and preliminary experimental verification performed in this study identified PTHLH as a potential target for the treatment of OA.

Background Fibroblast growth factor (FGF) and tumor growth factor-β (TGFβ) have emerged as pivotal regulators during the progression of osteosarcoma (OS). LHX9 is one crucial transcription factor controlled by FGF, however, its function in OS has not been investigated yet. Methods The expression of LHX9, FRS2, BMP4, TGF-beta R1, SMAD2, beta-catenin and metastasis-related proteins was measured by real-time quantitative PCR (RT-qPCR) and Western blot. CCK-8 assay and colony formation assay were employed to determine the proliferation of OS cells, while scratch wound healing assay and transwell assay were used to evaluate their migration and invasion, respectively. In vivo tumor growth and metastasis were determined by subcutaneous or intravenous injection of OS cells into nude mice. Results LHX9 expression was evidently up-regulated in OS tumor tissues and cell lines. Knockdown of LHX9 impaired the proliferation, migration, invasion and metastasis of OS cells. Mechanistically, LHX9 silencing led to the down-regulation of BMP-4, β-catenin and metastasis-related proteins, which was also observed in beta-catenin knockdown OS cells. By contrast, FRS2 knockdown conduced to the up-regulation of LHX9, BMP4, β-catenin and TGF-βR1, while TGF-beta inhibition repressed the expression of LHX9 and metastasis-related proteins. Additionally, let-7c modulates LHX9 and metastasis-related proteins by suppressing TGF-beta R1 expression on transcriptional level. Conclusions This study revealed LHX9 was essential for the proliferation, migration, invasion, and metastasis of OS cells via FGF and TGF-β/β-catenin signaling pathways.

Background. The aim of this study was to investigate the application of computer-aided design and 3D printing technology for percutaneous fixation of femoral neck fractures using cannulated compression screws. Methods. Using computed tomography data, an individualized proximal femur model was created with a 3D printer. The reduction of the femoral neck fracture and the placement of the cannulated compression screws were simulated on a computer. A 3D printing guide plate was designed to match the proximal femur. After demonstrating the feasibility of the 3D model before the surgical procedure, the guide needles and cannulated compression screws were inserted with the aid of the 3D-printed guide plate. Results. During the procedure, the 3D-printed guide plate for each patient matched the bone markers of the proximal femur. With the aid of the 3D-printed guide plate, three cannulated compression screws were accurately inserted into the femoral neck to treat femoral neck fractures. After screw placement, intraoperative X-ray examination showed results that were consistent with the preoperative design. The time taken to complete the procedure in the guide plate group was 35.3 ± 2.1 min , the intraoperative blood loss was 6.3 ± 2.8 mL , and X-ray fluoroscopy was only performed 9.1 ± 3.5 times. Postoperative radiographs showed adequate reduction of the femoral neck fractures. The entry point, entry direction, and length of the three cannulated compression screws were consistent with the preoperative design, and the screws did not penetrate the bone cortex. Conclusion. Using computer-aided design and 3D printing technology, personalized and accurate placement of cannulated compression screws can be realized for the treatment of femoral neck fractures. This technique can shorten the time required for the procedure and reduce damage to the femoral neck cortex, intraoperative bleeding, and the exposure of patients and healthcare staff to radiation.

Osteosarcoma represents the most prevailing primary bone tumor and the third most common cancer in children and adolescents worldwide. Among noncoding RNAs, circular RNAs (circRNAs) refer to a unique class in the shape of a covalently closed continuous loop with neither 5' caps nor 3'-polyadenylated tails, which are generated through back-splicing. Recently, with the development of whole-genome and transcriptome sequencing technologies, a growing number of circRNAs have been found aberrantly expressed in multiple diseases, including osteosarcoma. circRNA are capable of various biological functions including miRNA sponge, mediating alternatives, regulating genes at posttranscriptional levels, and interacting with proteins, indicating a pivotal role of circRNA in cancer initiation, progression, chemoresistance, and immune response. Moreover, circRNAs have been thrust into the spotlight as potential biomarkers and therapeutic targets in osteosarcoma. Herein, we briefly summarize the origin and biogenesis of circRNA with current knowledge of circRNA in tumorigenesis of osteosarcoma, aiming to elucidate the specific role and clinical implication of circRNAs in osteosarcoma.

Background: OIP5-AS1 has been reported to be aberrantly expressed in multiple cancers and associated with clinical outcomes. We conducted this study to assess the generalized prognostic val...

Cartilage calcification contributes to the development and progression of osteoarthritis (OA). It has been well-investigated adiponectin regulates vascular calcification. The purpose of this study is to investigate the therapeutic value and the molecular mechanism of AdipoRon, an adiponectin receptor agonist, on the chondrocytes calcification. Primary chondrocytes were isolated and cultured from normal cartilage and OA cartilage. The calcification in tissues was evaluated by inductively coupled plasma/atomic emission spectroscopy and alizarin red S staining. The calcification in chondrocytes was determined using the alkaline phosphatase (ALP) staining and an ALP assay kit. The cellular effects of AdipoRon were assessed by immunofluorescence staining and Western blot analysis. We found that calcification was significantly increased in OA cartilage tissues and cells. Importantly, the degree of calcification and ALP activity of the OA chondrocytes was decreased upon the treatment with AdipoRon. The AdipoRon-induced cellular effects, including the reduction of the calcification of chondrocytes and improvement of autophagy, were blocked by dorsomorphin, an 5'-adenosine monophosphate-activated protein kinase (AMPK) inhibitor. Moreover, autophagy activation by AdipoRon was mediated by the AMPK-mammalian target of rapamycin (mTOR) signaling pathway. Our results suggest that AdipoRon significantly alleviates the calcification of OA chondrocytes via activating AMPK-mTOR signaling to promote autophagy. Therefore, AdipoRon could be a potential therapeutic agent for the prevention and treatment of OA.

Background and Aims. A growing body of research has demonstrated that the degeneration of chondrocytes is the primary cause of osteoarthritis (OA). Parathyroid hormone-related protein (PTHrP) can alleviate the degeneration of chondrocytes via promotion of chondrocyte proliferation and inhibition of terminal differentiation, but the underlying mechanism remains unknown. This study aimed to identify the microRNAs (miRNAs) that may target PTHrP and regulate the proliferation and terminal differentiation of chondrocytes. Methods. Bioinformatic analysis was used to predict which miRNAs target PTHrP. We collected human knee cartilage specimens to acquire the primary chondrocytes, which we then used to test the expression and function of the targeted miRNAs. To explore the effects of miR-15a-5p on the putative binding sites, specific mimics or inhibitors were transfected into the chondrocytes. Furthermore, a dual-luciferase reporter gene assay and chondrocyte degeneration-related factors were used to verify the possible mechanism. Results. The expression of PTHrP was upregulated in the OA chondrocytes, whilst miR-15a-5p was downregulated in the OA chondrocytes. A negative correlation was observed between PTHrP and miR-15a-5p. The knockdown of miR-15a-5p promoted the growth of chondrocytes and inhibited calcium deposition, whilst overexpression of miR-15a-5p reversed this trend. The effect of miR-15a-5p overexpression was neutralised by PTHrP. Dual-luciferase reporter assays revealed that PTHrP can be used as a novel targeting molecule for miR-15a-5p. Conclusions. miR-15a-5p promotes the degeneration of chondrocytes by targeting PTHrP and, in addition to helping us understand the development of OA, may be a potential biomarker of OA.