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Modular femoral components can improve hip function, provide distal fixation, equalize leg length, and result in fewer complications when used to revise failed femoral components.

Abstract. 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 microRNA-145 (miRNA/miR-145) has previously been identified to be associated with the aggressiveness and metastasis of OS. However, the detailed regulatory mechanism by which miR-145 inhibits OS remains largely unknown. The present study demonstrated that miR-145 was significantly downregulated in OS tissues and KHOS and U2OS cell lines. Rho-associated protein kinase 1 (ROCK1), a key regulator of actin cytoskeleton reorganization, was identified as a novel target of miR-145. Ectopic expression of miR-145 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 miR-145 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, miRNA-145 inhibits OS cell proliferation and invasion, at least in part by directly targeting ROCK1. These results indicate that miR-145 may be a potential candidate for the diagnosis and treatment of OS. IntroductionOsteosarcoma (OS) mainly arises from the metaphysis of the long bones of adolescents and young adults. OS is the most common primary malignant tumor and is associated with high morbidity (1). Despite wide tumor excision combining multi-agent chemotherapy and radiotherapy, the five-year survival rate of patients with recurrent or metastatic OS remains at ~30% (2). Although recent studies have focused on the molecular pathogenesis of OS (3), its detailed molecular mechanisms have not been fully elucidated. As a result, the identification of novel molecular candidates and/or targets is crucial for the development of effective therapeutic strategies to improve the prognosis of OS.microRNAs (miRNA/miRs) are small non-coding RNA molecules with 18-25 nucleotides, which mainly negatively regulate gene expression by suppressing translation via binding to the 3' untranslated region (3'UTR) of their target genes (4). Previously, miRNAs have been demonstrated to have crucial roles in various physiological and pathological processes, including the development and progression of malignant tumors (5). In fact, it has been demonstrated that miRNAs function as oncogenes or tumor suppressors in cellular proliferation, apoptosis, differentiation, migration and invasion in various cancer cells (6,7). Despite indications that several miRNAs, including miR-20a, miR-199a-3p, miR-143 and so forth, are involved in the development and progression of OS (8-10), their exact role remains largely unknown. Previously, miR-145 was identified as a tumor-suppressive miRNA in multiple types of cancers, including lung, glioma, ovarian, colon, gastric, bladder, prostate and breast cancer, ...

BackgroundIn the ultrahigh molecular weight polyethylene (UHMWPE) prosthetic environment, fibroblasts affected by wear particles have the capacity of osteogenesis to reduce osteolysis. We aimed to assess the effects of macrophages on the osteogenic capability of fibroblasts treated with UHMWPE wear particles.MethodsThe effect of different concentrations of UHMWPE (0, 0.01, 0.1, and 1 mg/ml, respectively) on macrophage proliferation were validated by MTT assay to determine the optimum one. The fibroblasts viability was further determined in the co-culture system of UHMWPE particles and macrophage supernatants. The experiment was designed as seven groups: (A) fibroblasts only; (B) fibroblasts + 1 mg/ml UHMWPE particles; and (C1–C5) fibroblasts + 1/16, 1/8, 1/4, 1/2, and 1/1 supernatants of macrophage cultures stimulated by 1 mg/ml UHMWPE particles vs. fibroblast complete media, respectively. Alizarin red staining was used to detect calcium accumulation. The expression levels of osteogenic proteins were detected by Western blot and ELISA, including alkaline phosphatase (ALP) and osteocalcin (OCN).ResultsThe concentration of 0.1 mg/ml was considered as the optimum concentration for macrophage proliferation due to the survival rate and was highest among the four concentrations. Fibroblast viability was better in the group of fibroblasts + 1/16 ratio of macrophage supernatants stimulated by 1 mg/ml of UHMWPE particles than the other groups (1:8, 1:4, 1:2, 1:1). ALP and OCN expressions were significantly decreased in the group of fibroblasts + 1/4, 1/2, and 1/1 supernatants stimulated by 1 mg/ml of UHMWPE particles compared with other groups (1/8, 1/16) and the group of fibroblasts + 1 mg/ml UHMWPE (p < 0.5).ConclusionsMacrophages are potentially involved in the periprosthetic osteolysis by reducing the osteogenic capability of fibroblasts treated with wear particles generated from UHMWPE materials in total hip arthroplasty.

Osteosarcoma is the most common type of cancer that develops in bone, mainly arising from the metaphysis of the long bones. MicroRNA (miR)-200b has been found to generally act as a tumor suppressor in multiple types of human cancers. However, the detailed role of miR-200b in osteosarcoma still remains to be fully understood. This study aimed to investigate the exact role of miR-200b in the progression of osteosarcoma and the underlying mechanism. Real-time reverse transcription-polymerase chain reaction data showed that miR-200b was significantly downregulated in osteosarcoma tissues compared to their matched adjacent nontumor tissues. Low miR-200b level was associated with the advanced clinical stage and positive distant metastasis. Besides, it was also downregulated in osteosarcoma cell lines (U2OS, Saos2, HOS, and MG63) compared to normal osteoblast cell line NHOst. In vitro study showed that restoration of miR-200b led to a significant decrease in proliferation, migration, and invasion of osteosarcoma cells. Moreover, ZEB1 was identified as a target gene of miR-200b, and its expression levels were negatively mediated by miR-200b in osteosarcoma cells. In addition, ZEB1 was significantly upregulated in osteosarcoma cells compared to the normal osteoblast cell line NHOst, and inhibition of ZEB1 expression also suppressed the proliferation, migration, and invasion in osteosarcoma cells. Finally, we showed that ZEB1 was frequently upregulated in osteosarcoma tissues compared to their matched adjacent normal tissues, and its expression was reversely correlated to the miR-200b levels in osteosarcoma tissues. Based on these findings, our study suggests that miR-200b inhibits the proliferation, migration, and invasion of osteosarcoma cells, probably via the inhibition of ZEB1 expression. Therefore, miR-200b/ZEB1 may become a potential target for the treatment of osteosarcoma.

Abstract. Chondrosarcoma is one of the most common types of primary bone cancer that develops in cartilage cells. Resveratrol (Res), a natural polyphenol compound isolated from various fruits, has a suppressive effect on various human malignancies. It has been shown that Res inhibits matrix metalloproteinase (MMP)-induced differentiation in chondrosarcoma cells. However, the effects of Res on cell proliferation, apoptosis and invasion of chondrosarcoma cells, as well as the underlying mechanisms, remain largely unknown. To the best of our knowledge, the present study showed for the first time that Res inhibited proliferation and induced apoptosis in chondrosarcoma cells in a dose-dependent manner. Furthermore, it was shown that Res also suppressed chondrosarcoma cell invasion in a dose-dependent manner, probably via the inhibition of MMP2 and MMP9 protein expression. Molecular mechanism investigations revealed that Res could inhibit the activity of phosphoinositide 3-kinase/AKT and p38 mitogen-activated protein kinase signaling pathways, which has been demonstrated to be important in the regulation of proliferation, apoptosis and invasion in various cancer cell types. In conclusion, this study suggests that Res may serve as a promising agent for the treatment of chondrosarcoma.

Background Surgical resection and reconstruction for low-grade bone sarcoma in the metaphysis of the distal femur remain challenging. We hypothesized that 3D printing osteotomy guide plate could assist to accurately resect the tumor lesion and save the joint function. Methods From January 2017 to August 2019, five patients diagnosed with low-grade bone sarcoma in the metaphysis of the distal femur were treated with hemicortical resection using 3D printing guide plate. Autologous bone graft was inactivated in a high-temperature water bath and re-implanted in situ fixed with plate and screw. Patients were followed up from 17 to 33 months. The Musculoskeletal Tumor Society Score was used to evaluate the joint function. X-ray was used to evaluate the bone union. Results One patient was paracorticular osteosarcoma, and four cases had highly differentiated chondrosarcoma. All cases were involved in the metaphysis of the distal femur. Patients were followed up from 13 to 33 months, with an average of 23.6 months. There was neither post-operation infection, internal fixation loosening, nor fracture occurrence in any of the patients. The Musculoskeletal Tumor Society Score averaged at 28.1, while the International Society of Limb Salvage imaging score examination averaged 89.8%. Conclusions Here, we demonstrate that the 3D printing osteotomy guide plate-assisted hemicortical bone resection is a beneficial strategy to effectively resect the primary low-grade malignant bone tumors in the metaphysis of the distal femur and retained satisfied joint function.

The pathogenesis of periprosthetic osteolysis with septic loosening remains incompletely understood. The purpose of this study was to investigate whether expression of the RANKL/RANK/OPG system is altered in septic interface membranes (SIMs). Seventeen cases with a SIM, 26 cases with an aseptic interface membrane (AIM), and 12 cases with a normal synovium (NS) were assessed. Scanning and transmission electron microscopy (SEM and TEM, respectively) were used to observe the microscopic morphology of three tissue conditions. Differences in RANKL, RANK, and OPG expression at the mRNA level were assessed by real-time quantitative PCR, and differences at the protein level were assessed by immunohistochemical staining and Western blotting. SEM showed wear debris widely distributed on the AIM surface, and TEM showed Bacillus activity in the SIM. RANKL expression and the RANKL/OPG ratio were significantly increased in SIMs. Imbalance in the RANKL/RANK/OPG system is related to periprosthetic osteolysis with septic loosening but is not the only possible pathogenic mechanism.