UNASSIGNED: Aseptic loosening secondary to periprosthetic inflammatory @entity3061 results from the biological response to wear particles and is a leading cause of arthroplasty failure. The origin of this inflammatory response remains unclear. We aim to validate the definite link between endoplasmic reticulum (ER) stress and particle-induced inflammatory signaling pathways in @entity3564 . We examine the histopathologic changes of @entity3061 and the expression of specific biomarkers for ER-stress-mediated inflammatory signaling pathways ( @entity48354 , @entity13839 / @entity13839 , @entity9830 , NF-kB, ROS and @entity141 ). Moreover, pro-inflammatory cytokines ( @entity637 , @entity635 and @entity777 ) and osteoclastogenic molecules ( @entity1611 , @entity5271 , @entity5271 and @entity9827 ) were assessed in clinical interface membranes and @entity19 periosteum tissues. We found wear particles to be capable of inducing ER stress in macrophages within clinical osteolytic interface membranes and @entity19 osteolytic periosteum tissues and to be associated with the inflammatory response and osteoclastogenesis. Blocking ER stress with @entity10022 (4-PBA) results in a dramatic amelioration of particle-induced @entity3061 and a significant reduction of ER-stress intensity. Simultaneously, this ER-stress blocker also lessens inflammatory cell infiltration, diminishes the capability of osteoclastogenesis and reduces the inflammatory response by lowering @entity48354 , @entity13839 / @entity13839 , @entity9830 , NF-kB, ROS and @entity141 levels. Thus, ER stress plays an important role in particle-induced @entity32 . The pharmacological targeting of ER-stress-mediated inflammatory signaling pathways might be an appealing approach for alleviating or preventing particle-induced @entity3061 in at-risk @entity1 .

Endoplasmic reticulum stress-mediated inflammatory signaling pathways within the osteolytic periosteum and interface membrane in particle-induced XXXX .

@entity1 :: ('9606', 'Species') :: ['patients'] @entity32 :: ('MESH:D007249', 'Disease') :: ['inflammatory osteolysis and osteoclastogenic reactions'] @entity9827 :: ('12977(Tax:10090)', 'Gene') :: ['M-CSF'] @entity19 :: ('10090', 'Species') :: ['murine'] @entity635 :: ('16176(Tax:10090)', 'Gene') :: ['IL-1b'] @entity10022 :: ('MESH:C075773', 'Chemical') :: ['sodium 4-phenylbutyrate'] @entity5271 :: ('21943(Tax:10090)', 'Gene') :: ['OPG', 'RANKL'] @entity48354 :: ('78943(Tax:10090)', 'Gene') :: ['IRE1a'] @entity9830 :: ('14281(Tax:10090)', 'Gene') :: ['c-Fos'] @entity777 :: ('16193(Tax:10090)', 'Gene') :: ['IL-6'] @entity3061 :: ('MESH:D010014', 'Disease') :: ['osteolysis'] @entity141 :: ('CHEBI:29108', 'Chemical') :: ['Ca(2+)'] @entity1611 :: ('22339(Tax:10090)', 'Gene') :: ['VEGF'] @entity637 :: ('21926(Tax:10090)', 'Gene') :: ['TNF-a'] @entity13839 :: ('14828(Tax:10090)', 'Gene') :: ['GRP78', 'Bip'] @entity3564 :: ('MESH:D057068', 'Disease') :: ['periprosthetic osteolysis']
@entity3061 :: (MESH:D010014,Disease) :: ['osteolysis']
