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10.3389/fphar.2018.00647 http://scihub22266oqcxt.onion/10.3389/fphar.2018.00647 C6019442!6019442 !29973878     free     free     free Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 278.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 278.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 278.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 278.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\29973878 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Front+Pharmacol 2018 ; 9 (ä): 647 Nephropedia Template TP {{tp|p=29973878 |t=2018. 18?-Glycyrrhetinic Acid Inhibits Osteoclastogenesis In Vivo and In Vitro by Blocking RANKL-Mediated RANK-TRAF6 Interactions and NF-?B and MAPK Signaling Pathways |pdf=|usr=}}{{29973878 }} gab.com Text 18 -Glycyrrhetinic Acid Inhibits Osteoclastogenesis In Vivo and In Vitro by Blocking RANKL-Mediated RANK-TRAF6 Interactions and NF- B and MAPK Signaling Pathways JO: Front Pharmacol http://www.kidney.de/pget.php?&tw=1&pmid=29973878 #FOAvip Bone metabolism is determined by a delicate balance between bone resorption by osteoclasts and bone formation by osteoblasts. The imbalance due to over-activated osteoclasts plays an important role in various diseases. Activation of NF-?B and MAPK signaling pathways by receptor activator of nuclear factor -?B ligand (RANKL) is vital for osteoclastogenesis. Here, we for the first time explored the effects of 18?-glycyrrhetinic acid (18?-GA), a pentacyclic triterpenoid found in the Glycyrrhiza glabra L roots, on RANKL-induced osteoclastogenesis, osteoclast functions and signaling pathways in vitro and in vivo. In bone marrow monocytes (BMMs) and RAW264.7 cells, 18?-GA inhibited osteoclastogenesis, decreased expression of TRAP, cathepsin K, CTR and MMP-9, blocked actin ring formation and compromised osteoclasts functions in a dose-dependent manner at an early stage with minimal effects on osteogenic and adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). For underlying molecular mechanisms, 18?-GA inhibited RANKL-induced phosphorylation of p65, p50, and I?B, blocked p65 nuclear translocation and decreased the DNA-binding activity of NF-?B. Besides, 18?-GA inhibited the activation of the MAPK pathways. Co-immunoprecipitation showed that 18?-GA treatment blocked RANK-TRAF6 association at an upstream site. In vivo, 18?-GA treatment inhibited ovariectomy-induced osteoclastogenesis and reduced bone loss in mice. Overall, our results demonstrated that 18?-GA inhibited RANKL-induced osteoclastogenesis by inhibiting RANK expression in preosteoclasts and blocking the binding of RANK and TRAF6 which lead to the inhibition of NF-?B and MAPK signaling pathways. 18?-GA is a promising novel candidate in the treatment of osteoclast-related diseases such as postmenopausal osteoporosis. Twit Text FOAVip 18 -Glycyrrhetinic Acid Inhibits Osteoclastogenesis In Vivo and In Vitro by Blocking RANKL-Mediated RANK-TRAF6 Interactions and NF- B and MAPK Signaling Pathways ????Front Pharmacol http://www.kidney.de/pget.php?&tw=1&pmid=29973878 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=29973878 #FOAvip English Wikipedia <ref>{{Cite pmid|29973878 }}</ref> 18?-Glycyrrhetinic Acid Inhibits Osteoclastogenesis In Vivo and In Vitro by Blocking RANKL-Mediated RANK-TRAF6 Interactions and NF-?B and MAPK Signaling Pathways #MMPMID29973878 Chen X ; Zhi X ; Yin Z ; Li X ; Qin L ; Qiu Z ; Su J Front Pharmacol 2018[]; 9 (ä): 647 PMID29973878 show ga Bone metabolism is determined by a delicate balance between bone resorption by osteoclasts and bone formation by osteoblasts. The imbalance due to over-activated osteoclasts plays an important role in various diseases. Activation of NF-?B and MAPK signaling pathways by receptor activator of nuclear factor -?B ligand (RANKL) is vital for osteoclastogenesis. Here, we for the first time explored the effects of 18?-glycyrrhetinic acid (18?-GA), a pentacyclic triterpenoid found in the Glycyrrhiza glabra L roots, on RANKL-induced osteoclastogenesis, osteoclast functions and signaling pathways in vitro and in vivo. In bone marrow monocytes (BMMs) and RAW264.7 cells, 18?-GA inhibited osteoclastogenesis, decreased expression of TRAP, cathepsin K, CTR and MMP-9, blocked actin ring formation and compromised osteoclasts functions in a dose-dependent manner at an early stage with minimal effects on osteogenic and adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). For underlying molecular mechanisms, 18?-GA inhibited RANKL-induced phosphorylation of p65, p50, and I?B, blocked p65 nuclear translocation and decreased the DNA-binding activity of NF-?B. Besides, 18?-GA inhibited the activation of the MAPK pathways. Co-immunoprecipitation showed that 18?-GA treatment blocked RANK-TRAF6 association at an upstream site. In vivo, 18?-GA treatment inhibited ovariectomy-induced osteoclastogenesis and reduced bone loss in mice. Overall, our results demonstrated that 18?-GA inhibited RANKL-induced osteoclastogenesis by inhibiting RANK expression in preosteoclasts and blocking the binding of RANK and TRAF6 which lead to the inhibition of NF-?B and MAPK signaling pathways. 18?-GA is a promising novel candidate in the treatment of osteoclast-related diseases such as postmenopausal osteoporosis. ä18?-Glycyrrhetinic Acid Inhibits Osteoclastogenesis In Vivo and In Vit(epmc).pdf DeepDyve Pubget Overpricing