Prostaglandins regulate the expression of fibroblast growth factor-2 in bone

We examined the effect of PGs, particularly PGF(2 alpha), on basic fibrobla st growth factor-2 (FGF-2) messenger RNA (mRNA) and protein in the rat oste oblastic cell line Pyla and in fetal rat calvariae. Py1a cells expressed mu ltiple FGF-2 mRNA transcripts. PGF(2 alpha) dose-dependently increased the 6-kb transcript at 6 h. The selective PGF(2 alpha) agonist, fluprostenol (F lup), was more potent than PGF(2 alpha). Phorbol myristate acetate (10(-6) M) also increased a 6-kb mRNA at 6 h. By immunofluorescence microscopy, Flu p increased perinuclear staining for FGF-2 protein at 6 h and nuclear label ing at 24 h. Immunogold labeling of calvariae revealed that treatment with Flup for 3 h caused a transition of FGF expression from matrix to cells and an increase in cytoplasmic labeling for FGF-2 protein in periosteal cells and in osteoblasts. After treatment with Flup for 24 h, nuclear labeling wa s marked in periosteal cells and in osteoblasts, and a further increase in cytoplasmic labeling for FGF-2 was noted in osteocytes, periosteal cells, a nd osteoblasts. We conclude that PGs can increase FGF-2 mRNA and protein in bone cells. Because the effect of Flup was mimicked by phorbol myristate a cetate, we hypothesize that PGs' regulation of FGF-2 is mediated by a PGF(2 alpha)-selcctive receptor acting through protein kinase C. Hence, effects of PGs on bone remodeling may be mediated, in part, by endogenous FGF-2.