Objective. To examine whether depsipeptide (FK228), a histone deacetylase (HDA) inhibitor, has inhibitory effects on the proliferation of synovial fibroblasts from rheumatoid arthritis (RA) patients, and to examine the effects of systemic administration of FK228 in an animal model of arthritis.Methods. Autoantibody-mediated arthritis (AMA) was induced in 19 male DBA/1 mice (6-7 weeks old); 10 of them were treated by intravenous administration of FK228 (2.5 mg/kg), and 9 were used as controls. The effects of FK228 were examined by radiographic, histologic, and immunohistochemical analyses and arthritis scores. RA synovial fibroblasts (RASFs) were obtained at the time of joint replacement surgery. In vitro effects of FK228 on cell proliferation were assessed by MTT assay. Cell morphology was examined by light and transmission electron microscopy. The effects on the expression of the cell cycle regulators p16INK4a and p21 WAF1/Cip1 were examined by real-time polymerase chain reaction and Western blot analysis. The acetylation status of the promoter regions of p16INK4a and p21 WAF1/Cip1 were determined by chromatin immunoprecipitation assay.Results. A single intravenous injection of FK228 (2.5 mg/ml) successfully inhibited joint swelling, synovial inflammation, and subsequent bone and cartilage destruction in mice with AMA. FK228 treatment induced histone hyperacetylation in the synovial cells and decreased the levels of tumor necrosis factor ␣ and interleukin-1␤ in the synovial tissues of mice with AMA. Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial hyperplasia, with excessive inflammatory cell infiltration in the joints, leading to erosion of the articular cartilage and marginal bone, with subsequent joint destruction (1). Despite an explosion of information over the last 2 decades, a detailed understanding of the mechanisms of synovial hyperplasia and inflammation is lacking. Recent reports have implicated rapid proliferation of synovial cells, overexpression of inflammatory genes, and impairment of apoptosis, which can allow the persistence of abnormal cells (2-4), in the disease process.Cyclin-dependent kinases (CDKs) are essential Dr.

RUNX-2 might have a role as a key downstream mediator of p38's ability to regulate mechanical stress-induced MMP-13 and ADAMTS-5 expression.

Osteochondral injuries remain difficult to repair. We developed a novel photo-cross-linkable furfurylamine-conjugated gelatin (gelatin-FA). Gelatin-FA was rapidly cross-linked by visible light with Rose Bengal, a light sensitizer, and was kept gelled for 3 weeks submerged in saline at 37°C. When bone marrow-derived stromal cells (BMSCs) were suspended in gelatin-FA with 0.05% Rose Bengal, approximately 87% of the cells were viable in the hydrogel at 24 h after photo-cross-linking, and the chondrogenic differentiation of BMSCs was maintained for up to 3 weeks. BMP4 fusion protein with a collagen binding domain (CBD) was retained in the hydrogels at higher levels than unmodified BMP4. Gelatin-FA was subsequently employed as a scaffold for BMSCs and CBD-BMP4 in a rabbit osteochondral defect model. In both cases, the defect was repaired with articular cartilage-like tissue and regenerated subchondral bone. This novel, photo-cross-linkable gelatin appears to be a promising scaffold for the treatment of osteochondral injury.

Background: Percutaneous needle biopsy has many advantages over open biopsy in the treatment of neoplasms. However, the accuracy of needle biopsy in the diagnosis of musculoskeletal lesions has not yet been established. Here, we evaluate the accuracy and limitations of the procedure for musculoskeletal lesions. Methods: The diagnoses of 163 needle biopsies (bone, 91; soft tissue, 72) performed on 157 consecutive patients using a Jamshidi needle or an Ostycut needle for bone lesions, or a Tru-cut needle for soft tissue lesions were compared with the final diagnoses made by open biopsy and/or a definitive operation. Results: One hundred forty-three specimens (88%) were determined to be adequate for histological examination. Obtaining undamaged cores from very hard bony lesions or sclerotic cyst walls proved difficult. A pathologist with experience in musculoskeletal lesions was able to differentiate malignant tumors from benign lesions in 97% of the cases (bone, 100%; soft tissue, 94%) and arrive at a specific diagnosis in 88% (bone, 96%; soft tissue, 78%) when adequate cores were obtained. Differentiating a well-differentiated liposarcoma from a benign lipoma and inflammatory lesions from benign tumorous conditions, was difficult. The overall accuracy was 77% (bone, 85%; soft tissue, 68%). There was no morbidity related to the procedure. Conclusion:The results indicate that needle biopsy is safe and accurate for diagnosing musculoskeletal lesions.

BackgroundEmerging evidence has suggested that circulating microRNAs (miRNAs) in body fluids have novel diagnostic and prognostic significance for patients with malignant diseases. The lack of useful biomarkers is a crucial problem of bone and soft tissue sarcomas; therefore, we investigated the circulating miRNA signature and its clinical relevance in osteosarcoma.MethodsGlobal miRNA profiling was performed using patient serum collected from a discovery cohort of osteosarcoma patients and controls and cell culture media. The secretion of the detected miRNAs from osteosarcoma cells and clinical relevance of serum miRNA levels were evaluated using in vitro and in vivo models and a validation patient cohort.ResultsDiscovery screening identified 236 serum miRNAs that were highly expressed in osteosarcoma patients compared with controls, and eight among these were also identified in the cell culture media. Upregulated expression levels of miR-17-5p and miR-25-3p were identified in osteosarcoma cells, and these were abundantly secreted into the culture media in tumor-derived exosomes. Serum miR-25-3p levels were significantly higher in osteosarcoma patients than in control individuals in the validation cohort, with favorable sensitivity and specificity compared with serum alkaline phosphatase. Furthermore, serum miR-25-3p levels at diagnosis were correlated with patient prognosis and reflected tumor burden in both in vivo models and patients; these associations were more sensitive than those of serum alkaline phosphatase.ConclusionsSerum-based circulating miR-25-3p may serve as a non-invasive blood-based biomarker for tumor monitoring and prognostic prediction in osteosarcoma patients.