title: Parthenolide reduces empty lacunae and osteoclastic bone surface resorption induced by polyethylene particles in a murine calvarial model of peri-implant osteolysis.
abstract: The study aimed to determine the effects of parthenolide (PAR) on bone volume (BV) and bone surface resorption as assessed by live-animal microcomputed tomography (μCT) and possible osteocyte death as indicated by empty lacunae histologically in polyethylene (PE) particle-induced calvarial osteolysis in mice. Baseline μCT scans were conducted 7 days preimplantation of 2 × 10(8) PE particles/mL over the calvariae (day 0). PAR at 1 mg/kg/day was subcutaneously injected on days 0, 4, 7, and 10. At day 14, BV and surface resorption was analyzed with μCT. Calvarial tissue was processed for histomorphometric osteocyte evaluation. Serum was analyzed for type-1 carboxy-terminal collagen crosslinks (CTX-1) and osteoclast associated receptor (OSCAR) levels by ELISA. PE significantly decreased BV (p = 0.0368), increased surface bone resorption area (p = 0.0022), and increased the percentage of empty lacunae (p = 0.0043). Interestingly, PAR significantly reduced the resorption surface area (p = 0.0022) and the percentage of empty osteocyte lacunae (p = 0.0087) in the PE-calvariae, but it did not affect BV, serum CTX-1 or OSCAR levels. The ability of PAR to inhibit PE-induced surface bone erosion may better reflect the in vivo situation, where bone resorption occurs on the surface at the bone-implant interface and may also be related to the role of osteocytes in this pathology.
authors.affiliation: Discipline of Anatomy and Pathology, School of Medical Sciences, The University of Adelaide, Adelaide, SA, Australia.|School of Medical Sciences, Universiti Sains Malaysia, Malaysia.
authors.forename: Muhamad S F
authors.initials: MS
authors.lastname: Zawawi
authors.affiliation: School of Dentistry, The University of Adelaide, Adelaide, SA, Australia.
authors.forename: Victor
authors.initials: V
authors.lastname: Marino
authors.affiliation: Medical Device Research Institute, School of Computer Science, Engineering and Mathematics, Flinders University, Clovelly Park, SA, Australia.
authors.forename: Egon
authors.initials: E
authors.lastname: Perilli
authors.affiliation: Discipline of Anatomy and Pathology, School of Medical Sciences, The University of Adelaide, Adelaide, SA, Australia.
authors.forename: Melissa D
authors.initials: MD
authors.lastname: Cantley
authors.affiliation: School of Pathology and Laboratory Medicine, The University of Western Australia, Crawley, WA, Australia.
authors.forename: Jiake
authors.initials: J
authors.lastname: Xu
authors.affiliation: Hospital for Special Surgery, New York, NY, USA.
authors.forename: P Edward
authors.initials: PE
authors.lastname: Purdue
authors.affiliation: Discipline of Anatomy and Pathology, School of Medical Sciences, The University of Adelaide, Adelaide, SA, Australia.
authors.forename: Anak A S S K
authors.initials: AA
authors.lastname: Dharmapatni
authors.affiliation: Discipline of Anatomy and Pathology, School of Medical Sciences, The University of Adelaide, Adelaide, SA, Australia.
authors.forename: David R
authors.initials: DR
authors.lastname: Haynes
authors.affiliation: Discipline of Anatomy and Pathology, School of Medical Sciences, The University of Adelaide, Adelaide, SA, Australia.
authors.forename: Tania N
authors.initials: TN
authors.lastname: Crotti
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000097:blood / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000473:pathology*; D024042:Collagen Type I / Q000097:blood; D006801:Humans; D051379:Mice; D023421:Models, Animal; D009929:Organ Size / Q000187:drug effects; D010003:Osteoarthritis / Q000097:blood / Q000473:pathology; D010010:Osteoclasts / Q000187:drug effects / Q000473:pathology*; D010014:Osteolysis / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000473:pathology; D010455:Peptides / Q000097:blood; D020959:Polyethylene / Q000009:adverse effects*; D019736:Prostheses and Implants / Q000009:adverse effects*; D011956:Receptors, Cell Surface / Q000097:blood; D012717:Sesquiterpenes / Q000494:pharmacology*; D012886:Skull / Q000000981:diagnostic imaging / Q000473:pathology*; D012995:Solubility; D055114:X-Ray Microtomography
chemical_list: D024042:Collagen Type I; C512828:OSCAR protein, human; C450519:Oscar protein, mouse; D010455:Peptides; D011956:Receptors, Cell Surface; D012717:Sesquiterpenes; C052929:collagen type I trimeric cross-linked peptide; C002669:parthenolide; D020959:Polyethylene
keywords: bone resorption; calvarial model; osteolysis; parthenolide; wear particles