IndraLab

"Previous work from the Safadi laboratory demonstrated that GPNMB can directly bind to CD44 in osteoclast precursor cells through docking studies and immunoprecipitation [XREF_BIBR]."

"A similar study from the same lab found that GPNMB can directly bind to CD44 in mesenchymal stem cells [XREF_BIBR]."

"Prabata et al. (30) also found that GPNMB could bind to CD44 to prohibit nuclear factor kappa-B (NF-κB), thus abate the inflammatory response of macrophages.GPNMB can also be cleaved into a soluble form that contains an ectodomain (ECD) and functions as a secreted cytokine (31)."

"The observations also provide instructions for a specific therapeutic strategy to precisely and timely interrupt this signaling pathway using agents that attenuate moDC function at the level of Wfdc21 and/or GPNMB and downstream basal ESC function at the level of GPNMB/CD44 signaling interactions."

"Mechanism studies revealed that GPNMB was bound to CD44, a receptor expressed on the NP cell surface."

"Mechanism studies revealed that GPNMB was bound to CD44, a receptor expressed on the NP cell surface."

"We note, however, that in macrophages GPNMB binding to CD44 instead inhibits the NF‐κB signaling pathway to decrease the inflammatory response [80]."

"These same moDC and GPNMB-CD44 control points worked directly in mouse and human basal-ESC organoids, but the findings were not yet extended to studies of human disease conditions."

"Prabata et al. ( xref ) also found that GPNMB could bind to CD44 to prohibit nuclear factor kappa-B (NF-κB), thus abate the inflammatory response of macrophages."

"The possible intersection of GPNMB-CD44 and MAPK13 signals should also serve to define the basis for selective stem cell control with improvements in efficacy and safety."

"To support this possible interaction with GPNMB and CD44 in human GBM, we separated GPNMB expression in primary GBM by the median into high vs. low expression levels and determined the CD44 expression."

"In the tumor context, whether GPNMB could bind with CD44 on the OSCC cells was further confirmed by our study."

"These results indicate that soluble GPNMB interacts with its functional receptor CD44 on OSCC cells."

"Mechanically, GPNMB functionally interacts with CD44 to induce EMT, as blocking CD44 expression by RNA interference, the effects of GPNMB-induced tumor cell migration, invasion and EMT turned to be no[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

"The analysis was set to detect significant interactions between basal cells and moDCs versus interactions between basal cells and tissue monocytes (which lack GPNMB expression), and it selected GPNMB-CD44 interaction as having maximal probability for cell-cell communication ( xref )."

"GPNMB is a transmembrane protein that is overexpressed in many cancers, such as melanoma, breast cancer, glioma, etc. [ 33 ]M Liguori et al. found that soluble GPNMB produced by macrophages binds to C[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

"GPNMB also binds to CD44 and to other receptors: EGFR and VEGFR [ xref – xref ]."

"Even though there seemed not to be a correlation by Cox Proportional-Hazard model, the interaction between GPNMB and CD44 resulted significant (not shown)."

"A similar study from the same lab found that GPNMB can directly bind to CD44 in mesenchymal stem cells [ xref ]."

"A more efficient strategy might be to block GPNMB-CD44 signaling."

"Even though there seemed not to be a correlation by Cox Proportional-Hazard model, the interaction between GPNMB and CD44 resulted significant (not shown)."

"With its extracellular heparin and integrin binding motifs, Gpnmb, expressed by both resident and newly-infiltrating tissue macrophages [ 4 , 9–11 ], binds other cell types via its receptors CD44 [ 12[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

"In the tumor context, whether GPNMB could bind with CD44 on the OSCC cells was further confirmed by our study."

"GPNMB on TAMs binds to the CD44 of tumor stem cells, eliciting a response of IL33, which is a proponent of CSC growth."

"Additionally, GPNMB inhibits the inflammatory response of astrocytes by binding to CD44R [76]."

"We note, however, that in macrophages GPNMB binding to CD44 instead inhibits the NF‐κB signaling pathway to decrease the inflammatory response [ xref ]."

"Intriguingly, Gong et al identified GPNMB as a hepatokine modulating fatty acid synthesis in adipose tissue. xref Indeed, recombinant GPNMB treatment induced the expression of lipogenic genes, such as Fasn , Srebp1c , Acc , Acs , Acc , Acl , and Lce in vitro and in vivo xref Mechanistically, the cleaved soluble form of GPNMB bound with membrane receptor CD44 in adipocytes, and activated downstream PI3K-AKT-mTORC1-Srebp1c pathway to promote de novo lipogenesis. xref As confirmation of its function, GPNMB-mediated phosphorylation of AKT and lipogenesis can be mainly blunted by silencing CD44 both in adipocytes and in HFD-fed mice. xref The function was further verified in several distinct mouse models, including administrated with recombinant GPNMB, AAV mediated overexpression or silencing of GPNMB in mice, and transgenic mice with enforced GPNMB expression (Alb-TgGPNMB). xref Moreover, injection of GPNMB neutralization antibody promotes cold-induced BAT activation, reverses pre-existing obesity in mice, dramatically stimulates glucose uptake in BAT, and improves systemic insulin sensitivity. xref These studies support that inhibition of GPNMB by neutralization antibody may warrant therapeutic application in metabolic disorders."