Prostaglandins regulate the expression of fibroblast growth factor-2 in bone.
We examined the effect of PGs, particularly PGF2alpha, on basic fibroblast growth factor-2 (FGF-2) messenger RNA (mRNA) and protein in the rat osteoblastic cell line Py1a and in fetal rat calvariae. Py1a cells expressed multiple FGF-2 mRNA transcripts. PGF2alpha dose-dependently increased the 6-kb transcript at 6 h. The selective PGF2alpha agonist, fluprostenol (Flup), was more potent than PGF2alpha. Phorbol myristate acetate (10(-6) M) also increased a 6-kb mRNA at 6 h. By immunofluorescence microscopy, Flup increased perinuclear staining for FGF-2 protein at 6 h and nuclear labeling 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 was marked in periosteal cells and in osteoblasts, and a further increase in cytoplasmic labeling for FGF-2 was noted in osteocytes, periosteal cells, and 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 acetate, we hypothesize that PGs' regulation of FGF-2 is mediated by a PGF2alpha-selective receptor acting through protein kinase C. Hence, effects of PGs on bone remodeling may be mediated, in part, by endogenous FGF-2.
Sabbieti
M G
MG
Universita degli Studi di Camerino, Departimento Di Scienze, Italy.
Marchetti
L
L
Abreu
C
C
Montero
A
A
Hand
A R
AR
Raisz
L G
LG
Hurley
M M
MM
D000818:Animals; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D002478:Cells, Cultured; D015237:Dinoprost / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D008186:Luteolytic Agents / Q000494:pharmacology; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D011453:Prostaglandins / Q000502:physiology*; D011461:Prostaglandins F, Synthetic / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D008186:Luteolytic Agents; D011453:Prostaglandins; D011461:Prostaglandins F, Synthetic; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2; C006326:fluprostenol; D015237:Dinoprost