Inhibition of leukotriene function can modulate particulate-induced changes in bone cell differentiation and activity

Anderson, Gail I., MacQuarrie, Robyn, Osinga, Chris, Chen, Ying Fang, Langman, Maxine and Gilbert, Robert (2001) Inhibition of leukotriene function can modulate particulate-induced changes in bone cell differentiation and activity. Journal of biomedical materials research. Part B, Applied biomaterials, 58 4: 406-414. doi:10.1002/jbm.1035

Author Anderson, Gail I.
MacQuarrie, Robyn
Osinga, Chris
Chen, Ying Fang
Langman, Maxine
Gilbert, Robert
Title Inhibition of leukotriene function can modulate particulate-induced changes in bone cell differentiation and activity
Journal name Journal of biomedical materials research. Part B, Applied biomaterials   Check publisher's open access policy
ISSN 1552-4973
Publication date 2001-04-04
Sub-type Article (original research)
DOI 10.1002/jbm.1035
Volume 58
Issue 4
Start page 406
End page 414
Total pages 9
Place of publication Hoboken, NJ, U.S.A
Publisher John Wiley & Sons
Language eng
Subject 0707 Veterinary Sciences
0799 Other Agricultural and Veterinary Sciences
Abstract Aseptic loosening remains the major problem facing arthroplasty longevity with particulates from component materials touted as the cause of periprosthetic osteolysis. Proposed mechanisms in aseptic bone loss include: increased resorption, increased differentiation of osteoclasts (and/or macrophages locally), and decreased osteoblastic bone formation. Leukotrienes participate in osteoclastic bone resorption. We investigated inhibiting leukotrienes synthesis, using ICI 230487, to ameliorate the effects of particulates on osteoclast pit formation and also assessed the effects of alendronate, a bisphosphonate, on pit formation. Three particulates were used: ultra high molecular weight polyethylene (UHMWPE), polymethylmethacrylate (PMMA) and hydroxyapatite (HA). Osteoclast resorption was increased with UHMWPE, PMMA, and HA particles. Interventions with alendronate and ICI 230487 reduced particulate-induced osteoclast resorption. Both ICI 230487 and alendronate reduced osteoclast numbers at higher doses. To assess the effect of particulates on osteoclast and macrophage differentiation, mouse bone marrow was cultured and stained for tartrate resistant acid phosphatase colonies (TRAP+, osteoclasts) and nonspecific esterase positive colonies (NSE+, macrophage precursors). Particulates increased both TRAP+ and NSE+ colony formation. These increases were inhibited by ICI 230487. Particulates also inhibited osteoblast function assessed by the development of mineralized nodules and alkaline phosphatase positive (AP+) colony area. ICI 230487 partly protected osteoblast function from this particulate effect. Blockade of leukotriene production may prove a useful therapeutic intervention for particulate-induced aseptic loosening by inhibiting resorptive activity, reducing the pro-inflammatory cell populations induced and recruited by these particulates, as well as ameliorating the negative effects of inflammatory mediators on osteoblast function.© 2001 John Wiley & Sons, Inc. J Biomed Mater Res (Appl Biomater) 58: 406-414, 2001
Keyword Differentiation
5- Lipoxygenase inhibitor
ICI 230487
ZM 230487
Wear debris
Engineering, Biomedical
Materials Science, Biomaterials
Osteoclast Differentiation Resorption
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Veterinary Science Publications
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Citation counts: TR Web of Science Citation Count  Cited 15 times in Thomson Reuters Web of Science Article | Citations
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Created: Tue, 04 Apr 2006, 21:02:29 EST