Leukotriene B4 stimulates osteoclastic bone resorption both in vitro and in vivo

Carlos Garcia, Brendan F. Boyce, James Gilles, Mark Dallas, Mei Qiao, Gregory R. Mundy, Lynda Bonewald

Research output: Contribution to journalArticle

91 Citations (Scopus)

Abstract

Upon activation, the enzyme 5-lipoxygenase converts arachidonic acid into principally three products, the peptidoleukotrienes, 5- hydroperoxyeicosatetraenoic acid (5-HETE) or the leukotriene B4. We have shown that the peptido-leukotrienes (known as LTC4, LTD4, or LTE4) and 5-HETE induce osteoclastic bone resorption and that receptors for LTD4 are present on isolated avian osteoclast-like cells. Here, we show the effects of the third metabolic product of the 5-lipoxygenase (5-LO) pathway of arachidonic acid metabolism, the leukotriene LTB4, on osteoclastic bone resorption both in vivo and in vitro. Because LTB4 production is increased in a number of inflammatory conditions, it may be an important contributor to the bone loss which occurs in these disorders. LTB4 increased osteoclastic bone resorption in vivo following local administration over the calvariae of normal mice and in vitro in organ cultures of neonatal mouse calvariae. When LTB4 was injected over the calvaria of mice, there was a significant increase in bone resorption, osteoclast numbers, and eroded surfaces. LTB4 also increased the formation of resorption lacunae by isolated neonatal rat osteoclasts. Greater potency was observed with LTB4 compared with the peptido-leukotriene LTD4. This is in contrast to prostaglandins of the E series, which are reported to inhibit isolated osteoclasts. Experiments using marrow cultures suggest that LTB4 stimulates bone resorption in part by enhancing the formation of osteoclasts.

Original languageEnglish (US)
Pages (from-to)1619-1627
Number of pages9
JournalJournal of Bone and Mineral Research
Volume11
Issue number11
StatePublished - Nov 1996
Externally publishedYes

Fingerprint

Leukotriene B4
Bone Resorption
Osteoclasts
Leukotrienes
Skull
Leukotriene D4
Arachidonate 5-Lipoxygenase
Leukotriene E4
Leukotriene C4
Acids
In Vitro Techniques
Organ Culture Techniques
Prostaglandins E
Bone Marrow
Bone and Bones
Enzymes

ASJC Scopus subject areas

  • Surgery

Cite this

Garcia, C., Boyce, B. F., Gilles, J., Dallas, M., Qiao, M., Mundy, G. R., & Bonewald, L. (1996). Leukotriene B4 stimulates osteoclastic bone resorption both in vitro and in vivo. Journal of Bone and Mineral Research, 11(11), 1619-1627.

Leukotriene B4 stimulates osteoclastic bone resorption both in vitro and in vivo. / Garcia, Carlos; Boyce, Brendan F.; Gilles, James; Dallas, Mark; Qiao, Mei; Mundy, Gregory R.; Bonewald, Lynda.

In: Journal of Bone and Mineral Research, Vol. 11, No. 11, 11.1996, p. 1619-1627.

Research output: Contribution to journalArticle

Garcia, C, Boyce, BF, Gilles, J, Dallas, M, Qiao, M, Mundy, GR & Bonewald, L 1996, 'Leukotriene B4 stimulates osteoclastic bone resorption both in vitro and in vivo', Journal of Bone and Mineral Research, vol. 11, no. 11, pp. 1619-1627.
Garcia C, Boyce BF, Gilles J, Dallas M, Qiao M, Mundy GR et al. Leukotriene B4 stimulates osteoclastic bone resorption both in vitro and in vivo. Journal of Bone and Mineral Research. 1996 Nov;11(11):1619-1627.
Garcia, Carlos ; Boyce, Brendan F. ; Gilles, James ; Dallas, Mark ; Qiao, Mei ; Mundy, Gregory R. ; Bonewald, Lynda. / Leukotriene B4 stimulates osteoclastic bone resorption both in vitro and in vivo. In: Journal of Bone and Mineral Research. 1996 ; Vol. 11, No. 11. pp. 1619-1627.
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