Lipoxygenase metabolites are mediators of PTH-dependent human osteoblast growth

Bone
D SömjenN Stern

Abstract

PTH-induced osteoblast proliferation may contribute to its anabolic effects in bone. Since PTH-dependent osteoblast-like cell (Ob) growth is mediated via protein kinase C (PKC) and MAP kinase-kinase (MEK) and since lipoxygenase (LO) products activate PKC in a number of cell types, we assessed the expression of LO pathways in primary human cultured Ob. Ob from pre- or post-menopausal women were cultured and were treated with PTH and assayed for the expression of 12-LO and both type I and type II 15-LO mRNA and for the release their enzymatic products, 12- and 15-hydroxyeicosatetraenoic acid (HETE). Cells were also treated with PTH for stimulation DNA synthesis. First, Ob express platelet type- 12-LO and both type I and type II 15-LO mRNA and release their enzymatic products, 12- and 15-hydroxyeicosatetraenoic acid (HETE). Second, in female Ob, PTH induced a rapid increase in 12-HETE (50 fold increase) and 15-HETE (80 fold increase) and increased the expression of 12-LO mRNA but not of the two isoforms of 15-LO. PTH as well as 12 and 15-HETE stimulated DNA synthesis in Ob. The LO inhibitor baicalein inhibited PTH-stimulated DNA synthesis, which was reversed in the presence of either 12- or 15-HETE. A PKC inhibitor (bisindolylmale...Continue Reading

References

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Citations

Jan 3, 2012·International Journal of Biological Sciences·Yaozong ZhangLin Chen
Mar 14, 2013·Journal of Endocrinological Investigation·D SomjenG H Posner
Feb 2, 2011·Pharmacology, Biochemistry, and Behavior·Morgana MorettiJoão Quevedo
Sep 4, 2021·Materials Science & Engineering. C, Materials for Biological Applications·Dongdong YaoYonggang Lv

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