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Synovitis in osteoarthritis (OA) is a very common condition. However, its underlying mechanism is still not well understood. This study aimed to explore the molecular mechanisms of synovitis in OA. The gene expression profile GSE82107 (downloaded from the Gene Expression Omnibus database) included 10 synovial tissues of the OA patients and 7 synovial tissues of healthy people. Subsequently, differentially expressed gene (DEG) analysis, GO (gene ontology) enrichment analysis, pathway analysis, pathway network analysis, and gene signal network analysis were performed using Gene-Cloud of Biotechnology Information (GCBI). A total of 1,941 DEGs consisting of 1,471 upregulated genes and 470 downregulated genes were determined. Genes such as PSMG3, LRP12 MIA-RAB4B, ETHE1, SFXN1, DAZAP1, RABEP2, and C9orf16 were significantly regulated in synovitis of OA. In particular, the MAPK signalling pathway, apoptosis, and pathways in cancer played the most important roles in the pathway network. The relationships between these pathways were also analysed. Genes such as NRAS, SPHK2, FOS, CXCR4, PLD1, GNAI2, and PLA2G4F were strongly implicated in synovitis of OA. In summary, this study indicated that several molecular mechanisms were implicated in the development and progression of synovitis in OA, thus improving our understanding of OA and offering molecular targets for future therapeutic advances.

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Pulmonary metastasis is the major challenge for clinical treatment of osteosarcoma patients. Recent studies indicated that visfatin, a 52kDa adipocytokine, can trigger the cell motility of various cancers, while its role in the progression of osteosarcoma remains not clear. Our present study revealed that visfatin can significantly promote the in vitro migration and invasion of osteosarcoma MG-63 and HOS cells and up regulate the expression of matrix metalloproteinase-2 (MMP-2) and fibronectin (FN). Furthermore, visfatin treatment also increased the expression of IL-6 in both MG-63 and HOS cells via a time dependent manner, while anti-IL-6 antibody can significantly attenuate visfatin induced cell invasion and up regulation of MMP-2 and FN. It suggested that up regulation of IL-6 mediated visfatin induced in vitro motility of osteosarcoma cells. Visfatin treatment can increase the phosphorylation of both p65 and ERK1/2 in MG-63 and HOS cells, while only the inhibitor of NF-κB, BAY 11-7082, can abolish visfatin induced up regulation of IL-6. BAY 11-7082 also attenuated visfatin induced upregulation of MMP-2 and FN in MG-63 cells. Western blot analysis revealed that visfatin treatment can significantly increase the phosphorylation of IκBα and IKKß in MG-63 cells. ACHP, the inhibitor of IKK-ß, blocked visfatin induced expression of IL-6 mRNA in both MG-63 and HOS cells. Collectively, our data suggested that visfatin can increase the motility of osteosarcoma cells via up regulation of NF-κB/IL-6 signals. It indicated that visfatin might be a potential therapeutic target of osteosarcoma treatment.

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BACKGROUND: The diagnosis and treatment of bone nonunion have been studied extensively. Diagnosis and treatment of nonunion are mainly performed based on the interpretation of clinico-radiographic findings, which depend on the clinician's experience and the degree of bone callus formation during the fracture-healing process. However, resolution may be compromised when the bone mineral content is <25%. A feasible method of monitoring bone-healing is therefore needed. We monitored a rabbit model of bone nonunion by regular radiographic examinations, QCT detection, and biomarker concentrations. MATERIALS AND METHODS: Twenty purebred New Zealand rabbits (10 male and 10 female, 5-6 months of age, 2.5-3.0 kg) were divided into bone defect Group (I) that 10 left radius bones underwent resection of 1.5 cm of mid-radius bone and bone fracture Group (II) that another 10 left radius bones underwent only mid-radius fracture. Quantitative computed tomography detection of bone mineral density (BMD) and serum markers of bone formation (osteocalcin [OC], bone-specific alkaline phosphatase) and bone resorption (C- and N-terminal telopeptides of type I collagen (NTX) and tartrate-resistant acid phosphatase 5b) were assayed. There are twenty rabbits (10 male and 10 females). The age was 5-6 months weighing 2.5-3.0 kg). The defect was created in middle 1/3 radius in 10 rabbits and fracture was created in middle 1/3 radius of 10 rabbits. RESULTS: BMD and NTX concentrations were significantly lower at 5 weeks postoperatively compared to the preoperative values and were significantly different between the two groups. OC showed no significant difference before and after surgery. CONCLUSIONS: BMD and NTX concentrations may be useful for early detection of bone nonunion in rabbits.

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The aim of the present study was to establish an experimental animal model of fracture nonunion, and to investigate the changes in serum biomarker concentrations in fracture nonunion. A total of 20 purebred New Zealand rabbits were divided into two group: A bone defect group and a bone fracture group. In the bone defect group, a 15-mm section of bone (including the periosteum) was removed from the mid-radius, and the medullary cavities were closed with bone wax. In the bone fracture group, the mid-radius was fractured. X-rays were taken and blood samples were collected preoperatively and at 2, 3, 4, 5, 6, 7, 8, 10 and 12 weeks after the surgical procedure. The serum concentrations of osteocalcin (OC) and bone-specific alkaline phosphatase (BSAP) served as markers of bone formation, and those of C-terminal telopeptide of type I collagen (CTX), N-terminal telopeptide of type I collagen (NTX) and tartrate-resistant acid phosphatase 5b (TRACP 5b) served as markers of bone resorption. The concentration levels of the markers were measured using a biotin double-antibody sandwich enzyme-linked immunosorbent assay. In the bone defect group, bone callus was observed on X-ray at 2 weeks in three rabbits and the bone calluses stabilized at 5 weeks; however, none of the bones had healed at 8 weeks. In the bone fracture group, the fracture line was distorted at 2 weeks and bone calluses formed at 6-8 weeks. In the bone defect group, the serum BSAP and TRACP 5b concentrations increased following the surgical procedure, peaked at 4 weeks, began to decrease at 5 weeks and stabilized after 6 weeks. The serum OC concentrations did not change significantly following the surgical procedure. The serum CTX concentrations fluctuated during the first 4 weeks, peaked at 5 weeks, then decreased and stabilized after 6 weeks. The serum NTX concentrations fluctuated during the first 4 weeks, were significantly lower at 5 weeks compared with the other time points and stabilized after 6 weeks. These results suggested that a bone nonunion model can be established in New Zealand rabbits by resecting a 15-mm section of bone from the mid-radius prior to bone wax blocking. Measurement of the serum BSAP, CTX, NTX, and TRACP 5b concentrations may be useful for the early detection of bone nonunion. The serum NTX concentrations changed significantly in rabbits with bone nonunion. Further studies are required in order to determine the feasibility of using serum NTX concentrations for the early diagnosis of bone nonunion.

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miRNA-22 (miR-22) has been showed to involve in a variety of cancers; however, the association between miR-22 expression level and the prognosis of osteosarcoma is also poorly unknown. Fifty-two patients with surgically resected paired osteosarcoma and non-neoplastic disease between 2008 and 2014 were involved in this study. Real-time PCR was performed to examine the expression level of miR-22 in osteosarcoma tissues and noncancerous bone tissues. Then the association between miR-22 expression and clinical-pathological parameters were further evaluated. Kaplan-Meier analysis and Cox proportional hazards regression models were explored to reveal the correlations of miR-22 expression with survival of patients. The results indicated that miR-22 was downregulated in osteosarcoma tissues in comparison with noncancerous bone tissues. In addition, there is statistically significance between miR-22 expression level and recurrence, metastasis, and chemotherapy response. The patients with lower miR-22 expression level had both poorer overall survival and disease-free survival. The multivariant analysis revealed that the miR-22 expression level and metastasis status are independent prognosis factors for osteosarcoma. In conclusion, miR-22 was downregulated in osteosarcoma and its expression level was correlated with a variety of important clinical-pathological parameters. Moreover, miR-22 may serve as a promising biomarker for predicting the prognosis of osteosarcoma.

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In order to compensate for the fact that direct current electrical fields could not reduce or correct spinal-cord edema after trauma, methylprednisolone was used 2 hr after spinal-cord injury to promote the efficacy of the direct current electrical field. Thirty-three dogs were randomly divided into three groups and their spinal cords were injured with the Allen method (weight-dropping technique). Group A, a control group; Group B, implantation of an electrical stimulator 6 hr after spinal-cord injury; and Group C, given an injection of a large dose of methylprednisolone 2 hr after injury. Electric stimulators were implanted into the dogs' bodies 6 hr post-injury. The nerve functions, evoked potential cortical somatosensory and three kinds of nerve morphometric changes, were observed 1 to 3 months after injury. The indexes of Groups B and C were much better than Group A (p<0.05). The results in Group C were better than in Group B. Differences were statistically significant. The combination of direct current electrical field and an injection of a large dose of methylpredwisolone could effectively treat spinal cord injury, promoting earlier recovery of nerve function.

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