5-lipoxygenase metabolites inhibit bone formation in vitro

Kathy Traianedes, Mark R. Dallas, I. Ross Garrett, Gregory R. Mundy, Lynda F. Bonewald

Research output: Contribution to journalArticle

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Abstract

The leukotrienes and peptido-leukotrienes are 5-lipoxygenase (5-LO) metabolites of arachidonic acid that appear to have unique effects on bone, distinct from those of the prostaglandins. Application of exogenous leukotrienes in vitro and in vivo results in increased osteoclast formation and bone resorption. While 5-LO metabolites of arachidonic acid clearly stimulate osteoclastic bone resorption, little is known concerning their effects on osteoblastic bone formation. We examined the effects of the 5-LO metabolites 5-HETE, the leukotriene LTB4 and, as representative of the peptido-leukotrienes, LTD4 on the formation of mineralized nodules of fetal rat calvarial cells in the presence of dexamethasone and recombinant human bone morphogenetic protein-2 (rhBMP-2). We also examined the effects of these 5-LO metabolites on alkaline phosphatase activity and cell proliferation in these cultures and the effects of 5-HETE and LTB4 on cultured explants of neonatal murine calvariae. We found that the bone-forming capacity of osteoblasts was impaired when cells were cultured in the presence of 5-LO metabolites. These data indicate that metabolites of the 5-LO pathway are negative regulators of bone formation. The continued presence of these metabolites in the bone environment might account, in part, for the bone loss associated with chronic inflammatory conditions.

Original languageEnglish (US)
Pages (from-to)3178-3184
Number of pages7
JournalEndocrinology
Volume139
Issue number7
DOIs
StatePublished - Jan 1 1998

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Arachidonate 5-Lipoxygenase
Osteogenesis
Leukotrienes
Bone and Bones
Leukotriene B4
Bone Resorption
Leukotriene D4
Osteoclasts
Osteoblasts
Skull
Dexamethasone
Prostaglandins
Alkaline Phosphatase
In Vitro Techniques
Cultured Cells
Cell Proliferation

ASJC Scopus subject areas

  • Endocrinology

Cite this

Traianedes, K., Dallas, M. R., Garrett, I. R., Mundy, G. R., & Bonewald, L. F. (1998). 5-lipoxygenase metabolites inhibit bone formation in vitro. Endocrinology, 139(7), 3178-3184. https://doi.org/10.1210/endo.139.7.6115

5-lipoxygenase metabolites inhibit bone formation in vitro. / Traianedes, Kathy; Dallas, Mark R.; Garrett, I. Ross; Mundy, Gregory R.; Bonewald, Lynda F.

In: Endocrinology, Vol. 139, No. 7, 01.01.1998, p. 3178-3184.

Research output: Contribution to journalArticle

Traianedes, K, Dallas, MR, Garrett, IR, Mundy, GR & Bonewald, LF 1998, '5-lipoxygenase metabolites inhibit bone formation in vitro', Endocrinology, vol. 139, no. 7, pp. 3178-3184. https://doi.org/10.1210/endo.139.7.6115
Traianedes, Kathy ; Dallas, Mark R. ; Garrett, I. Ross ; Mundy, Gregory R. ; Bonewald, Lynda F. / 5-lipoxygenase metabolites inhibit bone formation in vitro. In: Endocrinology. 1998 ; Vol. 139, No. 7. pp. 3178-3184.
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