Lysophosphatidic acid cooperates with 1α,25(OH)2D3 in stimulating human MG63 osteoblast maturation

J Gidley, S Openshaw, ET Pring, SL Sale, JP Mansell

Research output: Contribution to journalArticle (Academic Journal)peer-review

40 Citations (Scopus)

Abstract

Osteoblast maturation is partly controlled by the interaction of 1[alpha],25(OH)2D3 (D3), an active metabolite of Vitamin D, with other growth factors. The first reports describing the in vitro effect of D3 on human osteoblast differentiation performed experiments in the presence of serum. One potentially exciting candidate that might help explain the D3 responses observed for osteoblasts cultured with serum is lysophosphatidic acid (LPA). Drawn to the possibility that D3 and serum borne LPA might interact to induce osteoblast maturation we co-treated human cells with D3 and serum in the presence of Ki16425, an LPA receptor antagonist. Ki16425 inhibited osteoblast maturation as determined by markedly reduced alkaline phosphatase (ALP) expression. We subsequently found that LPA and D3 acted synergistically in generating mature osteoblasts and that this differentiation response could be inhibited using pertussis toxin, implying an important role of G[alpha]i signal transduction. Furthermore, we found evidence for a dependency on both mitogen activated protein kinase kinase (MEK) and Rho associated coiled kinase (ROCK) for LPA and D3 stimulated maturation.
Translated title of the contributionLysophosphatidic acid cooperates with 1α,25(OH)2D3 in stimulating human MG63 osteoblast maturation
Original languageEnglish
Pages (from-to)46 - 61
Number of pages16
JournalProstaglandins and other Lipid Mediators
Volume80 (1-2)
DOIs
Publication statusPublished - Jul 2006

Bibliographical note

Publisher: Elsevier

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