Platelet-derived growth factor stimulates the synthesis of interleukin-6 in cells of the osteoblast lineage.
Platelet-derived growth factor (PDGF) increases bone resorption and the number of osteoclasts in calvarial sections, and it may regulate local cytokines involved in bone remodeling. Interleukin-6 (IL-6), a cytokine secreted by osteoblasts, osteoclasts, and stromal cells, is known to increase osteoclast recruitment. We tested the effects of PDGF on IL-6 expression in cultures of osteoblast-enriched cells from 22-day-old fetal rat calvariae (Ob cells). Treatment of Ob cells with PDGF BB caused a time- and dose-dependent induction of IL-6 messenger RNA (mRNA), as determined by Northern blot analysis. The effect was maximal after 1 h of treatment and was observed with PDGF BB at 0.3-3.3 nM. Treatment with PDGF BB for 24 h also increased IL-6 polypeptide levels in the culture medium, as determined by a specific bioassay. Although PDGF AA increased IL-6 mRNA levels, its effect was less pronounced than that of PDGF BB. Phorbol 12-myristate 13-acetate (PMA) induced IL-6 transcripts, and the effect of PDGF BB was inhibited in the presence of the protein kinase C (PKC) inhibitor, sangivamycin, or after down-regulation of PKC by PMA preincubation. Although forskolin increased IL-6 mRNA levels, PDGF BB did not induce cAMP production in Ob cells. The calcium ionophore, ionomycin, enhanced IL-6 transcripts in Ob cells and the intracellular calcium chelator, 1,2-bis-(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetra-(acetoxymethyl)-ester, inhibited the induction of IL-6 transcripts by PDGF BB, PMA, and PTH. In conclusion, PDGF BB stimulates IL-6 expression in Ob cells, a response that is PKC and calcium dependent. The increase in IL-6 expression may be relevant to the actions of PDGF BB on bone resorption.
Franchimont
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N
Department of Research, Saint Francis Hospital and Medical Center, Hartford, Connecticut 06105, USA.
Canalis
E
E
D000818:Animals; D002478:Cells, Cultured; D005260:Female; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D010006:Osteoblasts / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D015850:Interleukin-6; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D013755:Tetradecanoylphorbol Acetate