Min Tu

Elevated osteopontin level of synovial fluid and articular cartilage is associated with disease severity in knee osteoarthritis patients

OBJECTIVE To investigate osteopontin (OPN) levels in both synovial fluid and articular cartilage of patients with primary knee osteoarthritis (OA) and their relationship with severity of the disease. METHOD Fifty patients aged 48-81 years with knee OA and 10 healthy controls were enrolled in this study. Anteroposterior knee radiographs or/and Mankin score were taken to determine the disease severity of the affected knee. The radiographic grading of OA in the knee was performed by using the Kellgren-Lawrence criteria. OPN levels in synovial fluid were measured using enzyme-linked immunosorbent assay. OPN levels in articular cartilage were assessed by immunohistochemical methods. RESULTS Compared to healthy controls, OA patients had higher OPN concentration in synovial fluid (4519.60+/-1830.37, 95%CI 3999.42-5039.79 vs 1179.70+/-303.39, 95%CI 1035.53-1438.74 pg/ml, P<0.001)and articular cartilage(0.6+/-0.06, 95%CI 0.59-0.62 vs 0.43+/-0.07, 95%CI 0.38-0.48, P<0.01). In addition, synovial fluid OPN levels showed a positive correlation with articular cartilage OPN levels (r=0.411, 95%CI 0.150-0.619, P=0.003). Subsequent analysis showed that synovial fluid OPN levels significantly correlated with severity of disease (Spearmans rho=0.581, 95%CI 0.335-0.726, P<0.001). Furthermore, the articular cartilage levels of OPN also correlated with disease severity (Spearmans rho=0.675, 95%CI 0.500-0.808, P<0.001). CONCLUSIONS OPN in synovial fluid and articular cartilage is associated with progressive joint damage and is likely to be a useful biomarker for determining disease severity and progression in knee OA.

Expression of synovial fluid and articular cartilage VIP in human osteoarthritic knee: a new indicator of disease severity?

OBJECTIVES Vasoactive intestinal peptide (VIP) is a molecule shared by the neuroendocrine immune network and is considered to be a potential candidate for treatment of inflammatory and autoimmune diseases. Although some recent studies demonstrate that VIP has a protective role in animal RA models, its variant in different disease grade of OA remains uncertain. DESIGN AND METHODS Fifty patients with primary knee OA and ten controls with severe trauma were enrolled. Synovial fluid and articular cartilage samples were collected from specimens of total knee arthroplasty (TKA) or knee above amputation. VIP levels in these samples were assessed by ELISA and immunohistochemistry. Kellgren-Lawrence criteria and Mankin score were taken to determine the disease severity. RESULTS Compared to the controls, OA patients have lower VIP concentration in synovial fluid (659.70±112.79, 95%CI 579.01-740.38 vs 470.83±156.40, 95%CI 426.38-515.28 pg/mL, P<0.001) and articular cartilage (0.26±0.02, 95%CI 0.24-0.28 vs 0.20±0.04, 95%CI 0.18-0.21, P<0.001). Subsequent analysis show that the VIP expression in synovial fluid is markedly correlated with its OD in articular cartilage (Pearsons r=0.580, P<0.001). Furthermore, the synovial fluid and articular cartilage levels of VIP both demonstrated to be negatively correlated with severity of disease (Spearmans ρ=0.838, P<0.001; Spearmans ρ=0.814, P<0.001). CONCLUSIONS VIP in synovial fluid and articular cartilage is negatively associated with progressive joint damage in OA and is a potential indictor of disease severity.

Correlation between senescence-associated beta-galactosidase expression in articular cartilage and disease severity of patients with knee osteoarthritis

The purposes of this study were to investigate senescence‐associated beta‐galactosidase (SA‐beta‐Gal) levels in articular cartilage of knee osteoarthritis (OA) and the relationship with severity of the disease.

MicroRNA-127-5p regulates osteopontin expression and osteopontin-mediated proliferation of human chondrocytes

The aim of this study was to determine the specific microRNA (miRNA) that regulates expression of osteopontin (OPN) in osteoarthritis (OA). The potential regulatory miRNAs for OPN messenger RNA (mRNA) were predicted by miRNA prediction programs. Among eight potential regulatory miRNAs, miR-220b, miR-513a-3p and miR-548n increased, while miR-181a, miR-181b, miR-181c, miR-181d and miR-127-5p decreased in OA patients. miRNA-127-5p mimics suppressed OPN production as well as the activity of a reporter construct containing the 3′-UTR of human OPN mRNA. In addition, mutation of miR-127-5p binding site in the 3′-UTR of OPN mRNA abolished miR-127-5p-mediated repression of reporter activity. Conversely, treatment with miR-127-5p inhibitor increased reporter activity and OPN production. Interestingly, miR-127-5p inhibited proliferation of chondrocytes through OPN. In conclusion, miRNA-127-5p is an important regulator of OPN in human chondrocytes and may contribute to the development of OA.

MicroRNA-200b acts as a tumor suppressor in osteosarcoma via targeting ZEB1

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.

Usefulness of specific OA biomarkers, thrombin-cleaved osteopontin, in the posterior cruciate ligament OA rabbit model

OBJECTIVE We undertook this study to determine whether thrombin-cleaved osteopontin (OPN) in synovial fluid (SF) represents a useful marker of osteoarthritis (OA) progression in the posterior cruciate ligament transection (PCLT) OA rabbit model. METHOD PCLT was performed on the right knee joints of 48 rabbits. The rabbits were then sacrificed separately at 4, 8, 16, and 24 weeks post-surgery, when the joint was harvested and macroscopic and histological assessments of articular cartilage were performed. Thrombin-cleaved OPN product in SF was determined using Western blotting and the levels were measured using an enzyme-linked immunoassay. RESULTS The macroscopic and histological scores for PCLT knees were already elevated 4 weeks after surgery and increased with time. Western blotting showed the presence of thrombin-cleaved OPN in SF from PCLT knees. Thrombin-cleaved OPN levels in SF were elevated at 4 weeks (P < 0.001) and were elevated peaking at 24 weeks (P < 0.00001) after PCLT compared to baseline. A positive significant correlation was found between thrombin-cleaved OPN levels and the macroscopic scores (8 weeks: ρ = 0.695, P = 0.012; 16 weeks: ρ = 0.751, P = 0.005; 24 weeks: ρ = 0.660, P = 0.020). Furthermore, the same correlation was noted between thrombin-cleaved OPN levels and the histological scores (4 weeks: ρ = 0.609, P = 0.036; 8 weeks: ρ = 0.662, P = 0.019; 16 weeks: ρ = 0.827, P = 0.001; 24 weeks: ρ = 0.813, P = 0.001). CONCLUSION In this rabbit model of PCLT, thrombin-cleaved OPN levels in SF appear to provide a useful marker of OA disease severity and progression.

Pathological and Therapeutic Aspects of Long Noncoding RNAs in Osteosarcoma

BACKGROUND Osteosarcoma (OS) is a common bone malignant tumor, which is the eighth leading form of pediatric cancer. Despite the modern chemotherapeutic development of OS, a number of patients with OS have a high risk of lung metastasis and local relapse after chemotherapy. OBJECTIVE This review study focused on the role of long non coding RNAs (lncRNAs) in OS progression, and presented update reports on OS treatment by targeting specific lncRNAs. METHOD We have acquired information on OS and lncRNAs from scientific databases like google scholar, pubmed and scopus, and reviewed for this study. RESULTS The lncRNAs regulate a number of biological processes, and abnormal expression of lncRNAs could play role in many cancers and other human diseases. Interestingly, some lncRNAs can act as oncogenes, while some act as tumor suppressor genes. A number of studies revealed that targeting the specific lncRNAs by RNA interferance technology may provide a novel therapeutic strategy in the treatment of OS. CONCLUSION LncRNAs could be a promising biomarker and might be a potential therapeutic target in OS patients.

Osteopontin Promotes Expression of Matrix Metalloproteinase 13 through NF-κB Signaling in Osteoarthritis

Osteopontin (OPN) is associated with the severity and progression of osteoarthritis (OA); however, the mechanism of OPN in the pathogenesis of OA is unknown. In this study, we found that OA patients had higher abundance of OPN and matrix metalloproteinase 13 (MMP13). In chondrocytes, we showed that OPN promoted the production of MMP13 and activation of NF-κB pathway by increasing the abundance of p65 and phosphorylated p65 and translocation of p65 protein from cytoplasm to nucleus. Notably, inhibition of NF-κB pathway by inhibitor suppressed the production of MMP13 induced by OPN treatment. In conclusion, OPN induces production of MMP13 through activation of NF-κB pathway.