✦ LIBER ✦

Tiludronate inhibits interleukin-6 synthesis in osteoblasts: Inhibition of phospholipase D activation in MC3T3-E1 cells

✍ Scribed by Haruhiko Tokuda; Osamu Kozawa; Atsushi Harada; Toshihiko Uematsu

Publisher: John Wiley and Sons
Year: 1998
Tongue: English
Weight: 82 KB
Volume: 69
Category: Article
ISSN: 0730-2312
DOI: 10.1002/(sici)1097-4644(19980601)69:3<252::aid-jcb3>3.0.co;2-q

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✦ Synopsis

In previous studies, we have reported that PGF 2␣ stimulates phosphoinositide hydrolysis by phospholipase C and phosphatidylcholine hydrolysis by phospholipase D through heterotrimeric GTP-binding protein in osteoblast-like MC3T3-E1 cells, and that PGF 2␣ and PGE 1 induce interleukin-6 (IL-6) synthesis via activation of protein kinase C and protein kinase A, respectively. In the present study, we investigated the effect of tiludronate, a bisphosphonate known to inhibit bone resorption, on the PGF 2␣ -and PGE 1 -induced IL-6 synthesis in these cells. Tiludronate significantly suppressed the PGF 2␣ -induced IL-6 secretion in a dose-dependent manner in the range between 0.1 and 30 µM. However, the IL-6 secretion induced by PGE 1 or (Bu) 2 cAMP was hardly affected by tiludronate. The choline formation induced by PGF 2␣ was reduced by tiludronate dose-dependently in the range between 0.1 and 30 µM. On the contrary, tiludronate had no effect on PGF 2␣ -induced formation of inositol phosphates. Tiludronate suppressed the choline formation induced by NaF, known as an activator of heterotrimeric GTP-binding protein. However, tiludronate had little effect on the formation of choline induced by TPA, a protein kinase C activator. Tiludronate significantly inhibited the NaF-induced IL-6 secretion in human osteoblastic osteosarcoma Saos-2 cells. These results strongly suggest that tiludronate inhibits PGF 2␣ -induced IL-6 synthesis via suppression of phosphatidylcholinehydrolyzing phospholipase D activation in osteoblasts, and that the inhibitory effect is exerted at the point between heterotrimeric GTP-binding protein and phospholipase D.

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