PMID- 26796208 OWN - NLM STAT- MEDLINE DCOM- 20161213 LR - 20220309 IS - 1878-7568 (Electronic) IS - 1742-7061 (Linking) VI - 33 DP - 2016 Mar TI - Evidence that osteocyte perilacunar remodelling contributes to polyethylene wear particle induced osteolysis. PG - 242-51 LID - S1742-7061(16)30015-0 [pii] LID - 10.1016/j.actbio.2016.01.016 [doi] AB - Periprosthetic osteolysis (PO) leading to aseptic loosening, is the most common cause of failure of total hip replacement (THR) in the mid- to long-term. Polyethylene (PE) particulates from the wear of prosthesis liners are bioactive and are implicated in the initiation and or progression of osteolysis. 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 PO by removing bone from their perilacunar matrix. Osteocyte responses to ultra-high molecular weight PE (UHMWPE) particles were examined in vitro in human primary osteocyte-like cultures, in vivo in the mouse calvarial osteolysis model, and in the acetabulum of patients undergoing revision total hip replacement (THR) surgery for PO. Osteocytes exposed to UHMWPE particles showed upregulated expression of catabolic markers, MMP-13, carbonic anhydrase 2 (CA2), cathepsin K (CTSK) and tartrate resistant acid phosphatase (TRAP), with no effect on cell viability, as assessed by Caspase 3 activity. Consistent with this catabolic activity causing perilacunar bone loss, histological analysis of calvarial sections from mice 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 patients with PO 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 patients. 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 aseptic loosening of orthopaedic implants. STATEMENT OF SIGNIFICANCE: This study addresses the clinical problem of periprosthetic osteolysis, bone loss in response to polyethylene wear particles derived from materials used in orthopaedic implants. Periprosthetic osteolysis 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 polyethylene particles stimulate another type of bone loss, mediated by the direct activity of bone mineral embedded osteocytes, termed osteocytic osteolysis or osteocyte perilacunar remodelling. This study provides new mechanistic insight into wear-particle mediated bone loss and represents a new paradigm for the way in which bone cells, namely osteocytes, the key controlling cell type in bone, react to biomaterials. CI - Copyright (c) 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. FAU - Ormsby, Renee T AU - Ormsby RT AD - Centre for Orthopaedic and Trauma Research, Discipline of Orthopaedics and Trauma, University of Adelaide, Adelaide, SA 5005, Australia. FAU - Cantley, Melissa AU - Cantley M AD - Discipline of Anatomy and Pathology, University of Adelaide, Adelaide, SA 5005, Australia; Myeloma Research Laboratory, SAHMRI, North Terrace, Adelaide, SA 5000, Australia. FAU - Kogawa, Masakazu AU - Kogawa M AD - Centre for Orthopaedic and Trauma Research, Discipline of Orthopaedics and Trauma, University of Adelaide, Adelaide, SA 5005, Australia. FAU - Solomon, L Bogdan AU - Solomon LB AD - Centre for Orthopaedic and Trauma Research, Discipline of Orthopaedics and Trauma, University of Adelaide, Adelaide, SA 5005, Australia. FAU - Haynes, David R AU - Haynes DR AD - Discipline of Anatomy and Pathology, University of Adelaide, Adelaide, SA 5005, Australia. FAU - Findlay, David M AU - Findlay DM AD - Centre for Orthopaedic and Trauma Research, Discipline of Orthopaedics and Trauma, University of Adelaide, Adelaide, SA 5005, Australia. FAU - Atkins, Gerald J AU - Atkins GJ AD - Centre for Orthopaedic and Trauma Research, Discipline of Orthopaedics and Trauma, University of Adelaide, Adelaide, SA 5005, Australia. Electronic address: gerald.atkins@adelaide.edu.au. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160118 PL - England TA - Acta Biomater JT - Acta biomaterialia JID - 101233144 RN - 0 (Polyethylenes) RN - 0 (ultra-high molecular weight polyethylene) SB - IM MH - Animals MH - Apoptosis/drug effects MH - Bone Resorption/pathology MH - Cell Differentiation/drug effects MH - Cell Survival/drug effects MH - Cells, Cultured MH - Gene Expression Regulation/drug effects MH - Humans MH - Mice MH - Models, Animal MH - Osteoblasts/drug effects/metabolism/pathology MH - Osteocytes/drug effects/metabolism/*pathology MH - Osteolysis/*chemically induced/genetics/pathology MH - Polyethylenes/*adverse effects MH - Skull/drug effects/pathology OTO - NOTNLM OT - Aseptic loosening OT - Osteocyte OT - Osteocytic osteolysis OT - Periprosthetic OT - Polyethylene OT - UHMWPE EDAT- 2016/01/23 06:00 MHDA- 2016/12/15 06:00 CRDT- 2016/01/23 06:00 PHST- 2015/08/28 00:00 [received] PHST- 2016/01/12 00:00 [revised] PHST- 2016/01/16 00:00 [accepted] PHST- 2016/01/23 06:00 [entrez] PHST- 2016/01/23 06:00 [pubmed] PHST- 2016/12/15 06:00 [medline] AID - S1742-7061(16)30015-0 [pii] AID - 10.1016/j.actbio.2016.01.016 [doi] PST - ppublish SO - Acta Biomater. 2016 Mar;33:242-51. doi: 10.1016/j.actbio.2016.01.016. Epub 2016 Jan 18.