BACKGROUND The receptor activator of NF-κB ligand (RANKL), a member of the TNF ligand superfamily, is known to regulate bone metabolism. The expression of each component of the RANK/RANKL/osteoprotegerin (OPG) system in the intervertebral disc (IVD) has not been examined in detail. The purposes of this study were to examine the expression of the RANK/RANKL/OPG system and to evaluate the functio...

INTRODUCTION IFN-gamma inducible protein-10 (CXCL10), a member of the CXC chemokine family, and its receptor CXCR3 contribute to the recruitment of T cells from the blood stream into the inflamed joints and have a crucial role in perpetuating inflammation in rheumatoid arthritis (RA) synovial joints. Recently we showed the role of CXCL10 on receptor activator of nuclear factor kappa-B ligand (R...

Purpose: Osteomodulin (OMD) is a Small Leucine Rich Proteoglycan (SLRP) highly specific of the bone extracellular matrix. Its production and expression are impaired in subchondral sclerosis associated with osteoarthritis (OA). This study aimed to investigate effects OMD on osteoblasts osteoclasts culture. Methods: Different concentrations (2.5, 10, 40 160 ng/ml), corresponding range concentrati...

The targeting of receptor activator of nuclear factor-κB ligand (RANKL) is being increasingly investigated as a potential therapeutic strategy in several types of cancers. However, the exact function and mechanism of RANKL in human endometrial cancer (EC), particularly in progesterone-resistant and aggressive EC, remain unclear. We evaluated whether targeting of RANKL might be an efficient ther...

Coupled bone turnover is directed by the expression of receptor-activated NFB ligand (RANKL) and its decoy receptor, osteoprotegerin (OPG). Proinflammatory cytokines, such as interleukin-1 (IL-1 ) and tumor necrosis factor(TNF) induce RANKL expression in bone marrow stromal cells. Here, we report that IL-1 and TNF-induced RANKL requires p38 mitogen-activating protein kinase (MAPK) pathway activ...

Recent findings have focused attention on the molecular consequences of the microenvironment in tumor progression, but events occurring in cancer cells themselves in response to their ambient conditions remain obscure. Here, we identify receptor activator of nuclear factor κB ligand (RANKL) as a microenvironment-specific factor essential for tumorigenesis in vivo, using head and neck squamous c...

BONE UNDERGOES A CONTINUous remodeling process, allowing optimal adaptation of microarchitecture to individual demands. Bone resorption triggered by osteoclasts is physiologically coupled and usually in balance with bone formation, which is mediated by osteoblasts. Recently, essential physiological interactions between osteoclasts and osteoblasts have been unraveled and the receptor activator o...

Excessive receptor activator of NF-kappaB ligand (RANKL) signaling causes enhanced osteoclast formation and bone resorption. Thus, down-regulation of RANKL expression or its downstream signals may be a therapeutic approach to the treatment of pathological bone loss. In this study, we investigated the effects of Trolox, a water-soluble vitamin E analogue, on osteoclastogenesis and RANKL signalin...

Vascular endothelial growth factor (VEGF) has angiogenic, inflammatory, and bone-destructive roles in rheumatoid arthritis (RA). We aimed to determine the unique role of VEGF in osteoclastogenesis in RA. VEGF-induced receptor activator of nuclear factor ҡB ligand (RANKL) expression was determined in RA synovial fibroblasts by real-time PCR, luciferase assays, and ELISA. Osteoclastogenesis in pe...

Receptor activator of nuclear factor κB ligand (RANKL) is critically involved in bone erosion of rheumatoid arthritis (RA). We previously reported association between younger age at onset of RA and a RANKL promoter SNP that conferred an elevated promoter activity via binding to a transcription factor SOX5. Here we study the regulation of SOX5 levels in relation to RANKL expression in RA synovia...