UNASSIGNED: @entity3564 ( @entity3564 ) leading to @entity1349 , is the most common cause of failure of total hip replacement (THR) in the mid- to long-term. @entity691 (PE) particulates from the wear of prosthesis liners are bioactive and are implicated in the initiation and or progression of @entity3061 . Evidence exists that cells of the osteoblast/osteocyte lineage are affected by PE particles and contribute to the catabolic response by promoting osteoclastic bone resorption. In this study, we hypothesised that osteocytes contribute directly to @entity3564 by removing bone from their perilacunar matrix. Osteocyte responses to ultra-high molecular weight PE (UHMWPE) particles were examined in vitro in @entity1 primary osteocyte-like cultures, in vivo in the @entity19 @entity3061 model, and in the acetabulum of @entity1 undergoing revision total hip replacement (THR) surgery for @entity3564 . Osteocytes exposed to UHMWPE particles showed upregulated expression of catabolic markers, @entity1550 , @entity7464 ( @entity7464 ), @entity3336 ( @entity3336 ) and tartrate resistant acid phosphatase (TRAP), with no effect on cell viability, as assessed by @entity522 activity. Consistent with this catabolic activity causing perilacunar @entity604 , histological analysis of calvarial sections from @entity19 exposed to UHMWPE revealed a significant (p<0.001) increase in osteocyte lacunar area (Lac.Ar) compared to sham-operated animals. Furthermore, acetabular biopsies from @entity1 with @entity3564 also showed significantly (p<0.001) increased osteocyte lacunar size in trabecular bone adjacent to PE particles, compared with osteocyte lacunar size in bone from primary THR @entity1 . Together, these findings suggest a previously unrecognised action of UHMWPE wear particles on osteocytes, which directly results in a loss of osteocyte perilacunar bone. This action may exacerbate the indirect pro-osteoclastic action of UHMWPE-affected osteocytes, previously shown to contribute to @entity1349 of orthopaedic implants. STATEMENT OF SIGNIFICANCE: This study addresses the clinical problem of @entity3564 , @entity604 in response to @entity691 wear particles derived from materials used in orthopaedic implants. @entity3564 has been thought to be due largely to wear particles stimulating the activity of bone resorbing osteoclasts. However, in this study we demonstrate for the first time that @entity691 particles stimulate another type of @entity604 , mediated by the direct activity of bone mineral embedded osteocytes, termed @entity3061 or @entity5707 . This study provides new mechanistic insight into wear-particle mediated @entity604 and represents a new paradigm for the way in which bone cells, namely osteocytes, the key controlling cell type in bone, react to biomaterials.

Evidence that XXXX contributes to @entity691 wear particle induced @entity3061 .

@entity691 :: ('MESH:D020959', 'Chemical') :: ['Polyethylene', 'polyethylene'] @entity1 :: ('9606', 'Species') :: ['human', 'patients'] @entity3336 :: ('1513', 'Gene') :: ['CTSK', 'cathepsin K'] @entity522 :: ('836', 'Gene') :: ['Caspase 3'] @entity19 :: ('10090', 'Species') :: ['mice', 'mouse'] @entity604 :: ('MESH:D016301', 'Disease') :: ['bone loss'] @entity7464 :: ('760', 'Gene') :: ['CA2', 'carbonic anhydrase 2'] @entity1550 :: ('4322', 'Gene') :: ['MMP-13'] @entity3061 :: ('MESH:D010014', 'Disease') :: ['osteocytic osteolysis', 'calvarial osteolysis', 'osteolysis'] @entity1349 :: ('MESH:D011475', 'Disease') :: ['aseptic loosening'] @entity5707 :: ('MESH:D020257', 'Disease') :: ['osteocyte perilacunar remodelling'] @entity3564 :: ('MESH:D057068', 'Disease') :: ['Periprosthetic osteolysis', 'PO', 'periprosthetic osteolysis']
@entity5707 :: (MESH:D020257,Disease) :: ['osteocyte perilacunar remodelling']
