Simvastatin inhibits cytokine‐stimulated Cyr61 expression in osteoblastic cells: A therapeutic benefit for arthritis

Abstract

Objective. To examine the effects of proinflammatory cytokines on Cyr61 expression in osteoblastic cells and the modulatory action of simvastatin, to assess the role of CREB in Cyr61 induction, and to investigate the relationship of osteoblastic expression of Cyr61 to disease progression in experimental arthritis.Methods. Cyr61 expression and CREB phosphorylation at serine 133 were examined by Western blotting. Promoter activity of Cyr61 was assessed by luciferase assay with promoter deletion/mutagenesis and forced expression/gene silencing of CREB. Interaction between CREB and the Cyr61 promoter was evaluated by electrophoretic mobility shift assay and chromatin immunoprecipitation. CCL2 expression was examined by Northern blotting and enzyme-linked immunosorbent assay. In rats with collagen-induced arthritis (CIA), osteoblastic expression of Cyr61 was examined by immunohistochemistry, and disease progression was assessed by clinical, radiographic, and histologic examination. Results. In primary human osteoblasts and U2OS

Simvastatin Alleviates the Progression of Periapical Lesions by Modulating Autophagy and Apoptosis in Osteoblasts

“…Active form of simvastatin was prepared according to the protocol described previously (11,17). Briefly, 25 mg of simvastatin was dissolved in 0.2 mL ethanol (95%-100%), followed by the addition of 0.3 mL NaOH.…”

CCN1, a Pro-Inflammatory Factor, Aggravates Psoriasis Skin Lesions by Promoting Keratinocyte Activation

“…CCN1 expression is regulated by the amount of certain agents, including cytokines, growth factors, hormone and some drugs. It has been reported that IL-17 enhances CCN1 production in fibroblast-like synoviocytes, TNF-α and IL-1β increases CCN1 production in human osteoblasts, and epidermal growth factor promotes CCN1 expression in human endometrial epithelial cells (Klein et al, 2012;Kok et al, 2011;Zhang et al, 2009).…”

CCN1 Promotes VEGF Production in Osteoblasts and Induces Endothelial Progenitor Cell Angiogenesis by Inhibiting miR-126 Expression in Rheumatoid Arthritis

“…VEGF is a major angiogenic factor in RA. (11,12) CCN1 is involved in RA pathogenesis (22) ; its effect on -F) MG-63 and hFOB cells were incubated with various concentrations of CCN1 (0 to 10 ng/mL) for 24 hours; VEGF expression was examined by qPCR, Western blot, and ELISA. (G-J) Cells were incubated with CCN1 (0 to 10 ng/mL) for 24 hours, or pretreated for 30 min with IgG control antibody or VEGF antibody (1 mg/mL), followed by stimulation with CCN1 (10 ng/mL) for 24 hours.…”

“…(21) Simvastatin inhibits CCN1 expression in RA synovial fibroblasts and alleviates RA, which suggests that CCN1 is important in the pathogenesis of RA. (22) A recent study has reported that VEGF is constitutively expressed in the subchondral bone and may be associated with osteoblasts. (23) However, the mechanism of interaction between CCN1 and VEGF during osteoblast angiogenesis remains unclear.…”