Retrovirus-Mediated Gene Transfer of Receptor Activator of Nuclear Factor-κB-Fc Prevents Bone Loss in Ovariectomized Mice

Stem Cells ◽  
2006 ◽  
Vol 24 (7) ◽  
pp. 1798-1805 ◽  
Author(s):  
Dohee Kim ◽  
Sun Wook Cho ◽  
Sun Ju Her ◽  
Jae Yun Yang ◽  
Sang Wan Kim ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Bone Loss ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Ovariectomized Mice ◽  
Receptor Activator

scholarly journals Lack of NOD2 attenuates ovariectomy-induced bone loss via inhibition of osteoclasts

2017 ◽  
Vol 235 (2) ◽  
pp. 85-96 ◽  
Author(s):  
Ke Ke ◽  
Ok-Joo Sul ◽  
Soo-Wol Chung ◽  
Jae-Hee Suh ◽  
Hye-Seon Choi
Keyword(s):  
Bone Loss ◽  
Nuclear Factor Kappa B ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Nuclear Factor Κb ◽  
Innate Immune ◽  
Nuclear Factor ◽  
Oxygen Species ◽  
Receptor Activator ◽  
Recognition Receptor ◽  
Oligomerization Domain

Nucleotide-binding oligomerization domain-2 (NOD2) is a pattern recognition receptor of the innate immune system. It interacts with serine–threonine kinases to induce activation of nuclear factor κB (NF-κB), which is important for receptor activator of nuclear factor kappa-B ligand (RANKL) signaling. We tested the idea that NOD2 modulates bone metabolism via an action on osteoclasts (OCs). The absence of NOD2 reduced ovariectomy-induced bone loss in mice, and lowered the area and the activity of OCs, by impairing RANKL signaling. It also reduced the level of reactive oxygen species (ROS), as well as of NF-κB-DNA binding upon RANKL exposure. NOD2 was found to physically interact with nicotinamide adenine dinucleotide phosphate oxidase 1, and this led to increased production of ROS in OCs. Our data suggest that NOD2 contributes to bone loss in estrogen deficiency by elevating ROS levels in OCs.

scholarly journals Therapeutic efficacy of soluble receptor activator of nuclear factor-κB-Fc delivered by nonviral gene transfer in a mouse model of osteolytic osteosarcoma

2008 ◽  
Vol 7 (10) ◽  
pp. 3389-3398 ◽  
Author(s):  
François Lamoureux ◽  
Gaëlle Picarda ◽  
Julie Rousseau ◽  
Clothilde Gourden ◽  
Séverine Battaglia ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Mouse Model ◽  
Therapeutic Efficacy ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Soluble Receptor ◽  
Nonviral Gene Transfer ◽  
Receptor Activator

scholarly journals T-cell receptor activator of nuclear factor-κB ligand/osteoprotegerin imbalance is associated with HIV-induced bone loss in patients with higher CD4+ T-cell counts

AIDS ◽  
2018 ◽  
Vol 32 (7) ◽  
pp. 885-894 ◽  
Author(s):  
Kehmia Titanji ◽  
Aswani Vunnava ◽  
Antonina Foster ◽  
Anandi N. Sheth ◽  
Jeffrey L. Lennox ◽  
...  
Keyword(s):  
T Cell ◽  
Bone Loss ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Nuclear Factor Κb ◽  
Cd4 T Cell ◽  
Nuclear Factor ◽  
Cell Counts ◽  
Receptor Activator

scholarly journals Prolactin blocks the expression of receptor activator of nuclear factor κB ligand and reduces osteoclastogenesis and bone loss in murine inflammatory arthritis

2017 ◽  
Vol 19 (1) ◽  
Author(s):  
Maria G. Ledesma-Colunga ◽  
Norma Adán ◽  
Georgina Ortiz ◽  
Mariana Solís-Gutiérrez ◽  
Fernando López-Barrera ◽  
...  
Keyword(s):  
Bone Loss ◽  
Inflammatory Arthritis ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Receptor Activator

scholarly journals The Fungal Metabolite (+)-Terrein Abrogates Ovariectomy-Induced Bone Loss and Receptor Activator of Nuclear Factor-κB Ligand–Induced Osteoclastogenesis by Suppressing Protein Kinase-C α/βII Phosphorylation

2021 ◽  
Vol 12 ◽  
Author(s):  
Kyosuke Sakaida ◽  
Kazuhiro Omori ◽  
Masaaki Nakayama ◽  
Hiroki Mandai ◽  
Saki Nakagawa ◽  
...  
Keyword(s):  
Bone Loss ◽  
Bone Mass ◽  
Bone Metabolism ◽  
Osteoclast Differentiation ◽  
Nuclear Factor Κb ◽  
Common Disease ◽  
Mouse Bone Marrow ◽  
Nuclear Factor ◽  
Receptor Activator

Osteoporosis is a common disease characterized by a systemic impairment of bone mass and microarchitecture that results in fragility fractures. Severe bone loss due to osteoporosis triggers pathological fractures and consequently decreases the daily life activity and quality of life. Therefore, prevention of osteoporosis has become an important issue to be addressed. We have reported that the fungal secondary metabolite (+)-terrein (TER), a natural compound derived from Aspergillus terreus, has shown receptor activator of nuclear factor-κB ligand (RANKL)–induced osteoclast differentiation by suppressing nuclear factor of activated T-cell 1 (NFATc1) expression, a master regulator of osteoclastogenesis. TER has been shown to possess extensive biological and pharmacological benefits; however, its effects on bone metabolism remain unclear. In this study, we investigated the effects of TER on the femoral bone metabolism using a mouse-ovariectomized osteoporosis model (OVX mice) and then on RANKL signal transduction using mouse bone marrow macrophages (mBMMs). In vivo administration of TER significantly improved bone density, bone mass, and trabecular number in OVX mice (p < 0.01). In addition, TER suppressed TRAP and cathepsin-K expression in the tissue sections of OVX mice (p < 0.01). In an in vitro study, TER suppressed RANKL-induced phosphorylation of PKCα/βII, which is involved in the expression of NFATc1 (p < 0.05). The PKC inhibitor, GF109203X, also inhibited RANKL-induced osteoclastogenesis in mBMMs as well as TER. In addition, TER suppressed the expression of osteoclastogenesis-related genes, such as Ocstamp, Dcstamp, Calcr, Atp6v0d2, Oscar, and Itgb3 (p < 0.01). These results provide promising evidence for the potential therapeutic application of TER as a novel treatment compound against osteoporosis.

scholarly journals Shikimic Acid Inhibits Osteoclastogenesis in Vivo and in Vitro by Blocking RANK/TRAF6 Association and Suppressing NF-κB and MAPK Signaling Pathways

2018 ◽  
Vol 51 (6) ◽  
pp. 2858-2871 ◽  
Author(s):  
Xiao Chen ◽  
Xiaoqun Li ◽  
Xiao Zhai ◽  
Xin Zhi ◽  
Liehu Cao ◽  
...  
Keyword(s):  
Bone Loss ◽  
Signaling Pathways ◽  
Shikimic Acid ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Bone Homeostasis ◽  
Actin Ring ◽  
Ovariectomized Mice

Background/Aims: Bone homeostasis is associated with the balance between bone-resorbing osteoclasts and bone-forming osteoblasts. Unbalanced bone homeostasis as a result of reduced osteogenesis or excessive osteoclastogenesis can lead to disorders such as osteoporosis, Paget’s disease, and rheumatoid arthritis. Shikimic acid is a cyclohexanecarboxylic acid, reported to exhibit pharmacological properties including anti-inflammatory and antioxidant activities. However, its effects on bone homeostasis remain unknown. Methods: First, the in vitro MTT cell viability assay was performed. Tartrate-resistant acid phosphatase (TRAP) and actin ring formation assays, as well as immunofluorescence staining were then performed to evaluate osteoclastogenesis. Potential signaling pathways were characterized by western blotting and verified in overexpression experiments. Related factors were examined by western blotting, reverse transcription polymerase chain reaction, electrophoretic mobility shift assay, and co-immunoprecipitation. Ovariectomized mice were used for the in vivo study. Results: TRAP staining showed that shikimic acid significantly inhibited osteoclastogenesis and pit resorption in bone marrow monocytes and RAW264.7 cells, and actin ring formation assays showed that shikimic acid suppressed the bone resorption function of osteoclasts. Furthermore, shikimic acid inhibited the receptor activator of nuclear factor-κB RANK/tumor necrosis factor receptor-associated factor 6 (TRAF6) association, suppressed nuclear factor-κB and mitogen-activated protein kinase signaling pathways, and downregulated nuclear factor of activated T-cell cytoplasmic 1. The expression of osteoclastogenesis biomarkers, including TRAF6, calcitonin receptor, TRAP, cathepsin K, and matrix metalloproteinase-9, was inhibited. In vivo, shikimic acid also significantly ameliorated bone loss and prevented osteoclastogenesis in ovariectomized mice. Conclusion: Shikimic acid inhibited osteoclastogenesis and osteoclast function by blocking RANK ligand-induced recruitment of TRAF6, as well as downstream signaling pathways in vitro. Shikimic acid also reduced ovariectomy-induced osteoclastogenesis and bone loss in vivo.

scholarly journals Receptor Activator of Nuclear Factor κB Ligand (RANKL) Protein Expression by B Lymphocytes Contributes to Ovariectomy-induced Bone Loss

2012 ◽  
Vol 287 (35) ◽  
pp. 29851-29860 ◽  
Author(s):  
Melda Onal ◽  
Jinhu Xiong ◽  
Xinrong Chen ◽  
Jeff D. Thostenson ◽  
Maria Almeida ◽  
...  
Keyword(s):  
Bone Loss ◽  
Protein Expression ◽  
B Lymphocytes ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Receptor Activator
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