scholarly journals Neogambogic Acid Suppresses Receptor Activator of Nuclear Factor κB Ligand (RANKL)-Induced Osteoclastogenesis by Inhibiting the JNK and NF-κB Pathways in Mouse Bone Marrow-Derived Monocyte/Macrophages

2018 ◽  
Vol 24 ◽  
pp. 2569-2577 ◽  
Author(s):  
Gu Jin ◽  
Fang-Fang Wang ◽  
Tao Li ◽  
Dong-Dong Jia ◽  
Yong Shen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Nuclear Factor Κb ◽  
Mouse Bone Marrow ◽  
Nuclear Factor ◽  
Receptor Activator

scholarly journals α-Lipoic acid suppresses osteoclastogenesis despite increasing the receptor activator of nuclear factor κB ligand/osteoprotegerin ratio in human bone marrow stromal cells

2005 ◽  
Vol 185 (3) ◽  
pp. 401-413 ◽  
Author(s):  
Jung-Min Koh ◽  
Young-Sun Lee ◽  
Chang-Hyun Byun ◽  
Eun-Ju Chang ◽  
Hyunsoo Kim ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Lipoic Acid ◽  
Nuclear Factor Κb ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Mouse Bone Marrow ◽  
Dependent Manner ◽  
Nuclear Factor ◽  
Receptor Activator ◽  
Dose Dependent

Growing evidence has shown a biochemical link between increased oxidative stress and reduced bone density. Although α-lipoic acid (α-LA) has been shown to act as a thiol antioxidant, its effect on bone cells has not been determined. Using proteomic analysis, we identified six differentially expressed proteins in the conditioned media of α-LA-treated human bone marrow stromal cell line (HS-5). One of these proteins, receptor activator of nuclear factor κB ligand (RANKL), was significantly up-regulated, as confirmed by immunoblotting with anti-RANKL antibody. ELISA showed that α-LA stimulated RANKL production in cellular extracts (membranous RANKL) about 5-fold and in conditioned medium (soluble RANKL) about 23-fold, but had no effect on osteoprotegerin (OPG) secretion. Despite increasing the RANKL/OPG ratio, α-LA showed a dose-dependent suppression of osteoclastogenesis, both in a coculture system of mouse bone marrow cells and osteoblasts and in a mouse bone marrow cell culture system, and reduced bone resorption in a dose-dependent manner. In addition, α-LA-induced soluble RANKL was not inhibited by matrix metalloprotease inhibitors, indicating that soluble RANKL is produced by α-LA without any posttranslational processing. In contrast, α-LA had no significant effect on the proliferation and differentiation of HS-5 cells. These results suggest that α-LA suppresses osteoclastogenesis by directly inhibiting RANKL–RANK mediated signals, not by mediating cellular RANKL production. In addition, our findings indicate that α-LA-induced soluble RANKL is not produced by shedding of membranous RANKL.

scholarly journals Interleukin-6 Inhibits Receptor Activator of Nuclear Factor κB Ligand-Induced Osteoclastogenesis by Diverting Cells into the Macrophage Lineage: Key Role of Serine727 Phosphorylation of Signal Transducer and Activator of Transcription 3

Endocrinology ◽  
2008 ◽  
Vol 149 (7) ◽  
pp. 3688-3697 ◽  
Author(s):  
Laurence Duplomb ◽  
Marc Baud’huin ◽  
Céline Charrier ◽  
Martine Berreur ◽  
Valérie Trichet ◽  
...  
Keyword(s):  
Osteoclast Differentiation ◽  
Nuclear Factor Κb ◽  
Mouse Bone Marrow ◽  
Nuclear Factor ◽  
Signal Transducer ◽  
Blood Monocytes ◽  
Receptor Activator ◽  
Few Data ◽  
Macrophage Lineage

Osteoclasts are bone-resorptive cells that differentiate from hematopoietic precursors upon receptor activator of nuclear factor κB ligand (RANKL) activation. Previous studies demonstrated that IL-6 indirectly stimulates osteoclastogenesis through the production of RANKL by osteoblasts. However, few data described the direct effect of IL-6 on osteoclasts. To investigate this effect, we used several models: murine RAW264.7 cells, mouse bone marrow, and human blood monocytes. In the three models used, the addition of IL-6 inhibited RANKL-induced osteoclastogenesis. Furthermore, IL-6 decreased the expression of osteoclast markers and up-modulated macrophage markers. To elucidate this inhibition, signal transducer and activator of transcription (STAT) 3, the main signaling molecule activated by IL-6, was analyzed. Addition of two STAT3 inhibitors completely abolished RANKL-induced osteoclastogenesis, revealing a key role of STAT3. We demonstrated that a basal level of phosphorylated-STAT3 on Serine727 associated with an absence of phosphorylation on Tyrosine705 is essential for osteoclastogenesis. Furthermore, a decrease of Serine727 phosphorylation led to an inhibition of osteoclast differentiation, whereas an increase of Tyrosine705 phosphorylation upon IL-6 stimulation led to the formation of macrophages instead of osteoclasts. In conclusion, we showed for the first time that IL-6 inhibits RANKL-induced osteoclastogenesis by diverting cells into the macrophage lineage, and demonstrated the functional role of activated-STAT3 and its form of phosphorylation in the control of osteoclastogenesis.

scholarly journals Mepazine Inhibits RANK-Induced Osteoclastogenesis Independent of Its MALT1 Inhibitory Function

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3144 ◽  
Author(s):  
Laura Meloni ◽  
Lynn Verstrepen ◽  
Marja Kreike ◽  
Jens Staal ◽  
Yasmine Driege ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Cathepsin K ◽  
Nuclear Factor Κb ◽  
Mouse Bone Marrow ◽  
Nuclear Factor ◽  
Activator Protein 1 ◽  
Knock Out ◽  
Inhibitory Function ◽  
Integral Role

Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is an intracellular cysteine protease (paracaspase) that plays an integral role in innate and adaptive immunity. The phenothiazine mepazine has been shown to inhibit the proteolytic activity of MALT1 and is frequently used to study its biological role. MALT1 has recently been suggested as a therapeutic target in rheumatoid arthritis. Here, we analyzed the effect of mepazine on the receptor activator of nuclear factor κ-B (RANK)-induced osteoclastogenesis. The treatment of mouse bone marrow precursor cells with mepazine strongly inhibited the RANK ligand (RANKL)-induced formation of osteoclasts, as well as the expression of several osteoclast markers, such as TRAP, cathepsin K, and calcitonin. However, RANKL induced osteoclastogenesis equally well in bone marrow cells derived from wild-type and Malt1 knock-out mice. Furthermore, the protective effect of mepazine was not affected by MALT1 deficiency. Additionally, the absence of MALT1 did not affect RANK-induced nuclear factor κB (NF-κB) and activator protein 1 (AP-1) activation. Overall, these studies demonstrate that MALT1 is not essential for RANK-induced osteoclastogenesis, and implicate a MALT1-independent mechanism of action of mepazine that should be taken into account in future studies using this compound.

scholarly journals Absence of Herpes Virus Entry Mediator (HVEM) Increases Bone Mass by Attenuating Receptor Activator of Nuclear Factor-κB ligand (RANKL)-Induced Osteoclastogenesis

Endocrinology ◽  
2012 ◽  
Vol 153 (10) ◽  
pp. 4808-4817 ◽  
Author(s):  
Woon-Ki Kim ◽  
Ok-Joo Sul ◽  
Eun-Kyung Choi ◽  
Mi-Hyun Lee ◽  
Choon-Soo Jeong ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Mass ◽  
Knockout Mice ◽  
Herpes Virus ◽  
Virus Entry ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Herpes Virus Entry Mediator ◽  
Receptor Activator ◽  
Herpès Virus

Abstract Herpes virus entry mediator (HVEM), which is constitutively expressed at a high level on myeloid lineage cells, is also expressed on bone marrow-derived macrophages, suggesting that it may play a role in bone metabolism by affecting osteoclasts (OC) derived from bone marrow-derived macrophages. To address this question, we evaluated bone mass by micro-computed tomography and the number and activity of OC by tartrate-resistant acid phosphatase (TRAP) and pit formation on dentine slices, comparing HVEM-knockout mice with wild-type mice. The absence of HVEM led to a higher bone mass and to decreased levels of serum collagen type I fragments and serum TRACP5b in vivo. In vitro HVEM deficiency resulted in a reduced number and activity of OC and an impaired receptor activator of nuclear factor-κB ligand signaling through reduced activation of nuclear factor-κB and of nuclear factor of activated T-cells cytoplasmic 1. Exogenous soluble HVEM decreased expression of TRAP, whereas soluble LIGHT (a ligand of HVEM) increased it, indicating the occurrence of a positive signaling through HVEM during osteoclastogenesis. Our findings indicate that HVEM regulates bone remodeling via action on OC. The higher bone mass in the femurs of HVEM-knockout mice could be, at least in part, due to attenuated osteoclastogenesis and bone resorption resulting from decreased receptor activator of nuclear factor-κB ligand signaling in the OC.

scholarly journals Role of Prostaglandin E in Receptor Activator of Nuclear Factor-κB Ligand (RANKL) Expression in Osteoblasts Induced by Cell Adhesion to Bone Marrow B-lymphocytes

2009 ◽  
Vol 55 (5) ◽  
pp. 832-837 ◽  
Author(s):  
Michiko Hirata ◽  
Suguru Harada ◽  
Chiho Matsumoto ◽  
Morichika Takita ◽  
Chisato Miyaura ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Adhesion ◽  
B Lymphocytes ◽  
Nuclear Factor Κb ◽  
Prostaglandin E ◽  
Nuclear Factor ◽  
Rankl Expression ◽  
Receptor Activator

MafB negatively regulates RANKL-mediated osteoclast differentiation

Blood ◽  
2006 ◽  
Vol 109 (8) ◽  
pp. 3253-3259 ◽  
Author(s):  
Kabsun Kim ◽  
Jung Ha Kim ◽  
Junwon Lee ◽  
Hye Mi Jin ◽  
Hyun Kook ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Transcription Factors ◽  
Phagocytic Activity ◽  
Osteoclast Differentiation ◽  
Nuclear Factor Κb ◽  
Osteoclast Formation ◽  
Nuclear Factor ◽  
Binding Ability ◽  
Receptor Activator ◽  
Macrophage Lineage

Abstract Receptor activator of nuclear factor κB ligand (RANKL) induces osteoclast formation from hematopoietic cells via regulation of various transcription factors. Here, we show that MafB negatively regulates RANKL-induced osteoclast differentiation. Expression levels of MafB are significantly reduced by RANKL during osteoclastogenesis. Overexpression of MafB in bone marrow-derived monocyte/macrophage lineage cells (BMMs) inhibits the formation of TRAP+ multinuclear osteoclasts, but phagocytic activity of BMMs is retained. Furthermore, overexpression of MafB in BMMs attenuates the gene induction of NFATc1 and osteoclast-associated receptor (OSCAR) during RANKL-mediated osteoclastogenesis. In addition, MafB proteins interfere with the DNA-binding ability of c-Fos, Mitf, and NFATc1, inhibiting their transactivation of NFATc1 and OSCAR. Furthermore, reduced expression of MafB by RNAi enhances osteoclastogenesis and increases expression of NFATc1 and OSCAR. Taken together, our results suggest that MafB can act as an important modulator of RANKL-mediated osteoclastogenesis.

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