Effects of basic fibroblast growth factor and a prostaglandin E2 receptor subtype 4 agonist on osteoblastogenesis and adipogenesis in aged ovariectomized rats.
bFGF stimulates osteo- and adipogenesis concurrently at skeletal sites with red but not with fatty marrow, whereas a PGE2 receptor subtype 4 agonist has bone anabolic effects at both skeletal sites and decreases adipose tissue within red and fatty marrow.


BACKGROUND
Basic fibroblast growth factor (bFGF) stimulates osteogenesis at skeletal sites with hematopoietic but not with fatty marrow. The prostaglandin E2 (PGE2) receptor subtype 4 agonist (EP4A) stimulates osteogenesis at the former skeletal sites, but its effects at fatty marrow sites are unknown. In addition, both bFGF and PGE2 through the EP4 receptor have also been implicated in adipogenesis. However, their specific effects on bone marrow adipogenesis and the inter-relationship with osteogenesis have never been studied in vivo.


METHODS
Female Sprague-Dawley rats were ovariectomized (OVX) or sham-operated and maintained for 1 yr after surgery. OVX rats were then injected daily with bFGF or with EP4A SC for 3 wk. The osteo- and adipogenic effects of these agents were assessed by histomorphometry and by determining changes in expression of genes associated with these events by real-time PCR in the lumbar and caudal vertebrae, bones with a predominance of hematopoietic and fatty marrow, respectively. Expression of FGFR1-4 and the EP4 receptor were also evaluated by real-time PCR and immunocytochemistry.


RESULTS
bFGF and EP4A stimulated bone formation at skeletal sites with hematopoietic marrow, but only the later anabolic agent is also effective at fatty marrow sites. The diminished bone anabolic effect of bFGF at the fatty marrow site was not caused by a lack of cell surface receptors for the growth factor at this site. Interestingly, whereas EP4A decreased fatty marrow area and the number of adipocytes, bFGF increased osteogenesis and adipogenesis within the bone marrow.


CONCLUSIONS
bFGF can stimulate osteogenesis and bone marrow adipogenesis concurrently at red marrow sites, but not at fatty marrow sites. In contrast, EP4A stimulates bone formation at skeletal sites with hematopoietic and fatty marrow and simultaneously decreased fatty marrow area and the number of adipocytes in the bone marrow, suggesting that osteogenesis occurs at the expense of adipogenesis.
Aguirre
J Ignacio
JI
Department of Physiological Sciences, University of Florida, Gainesville, Florida 32610, USA. aguirrej@mail.vetmed.ufl.edu
Leal
Martha E
ME
Rivera
Mercedes F
MF
Vanegas
Sally M
SM
Jorgensen
Marda
M
Wronski
Thomas J
TJ
D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002113:Calcification, Physiologic / Q000187:drug effects; D024042:Collagen Type I / Q000235:genetics; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006400:Hematocrit; D008159:Lumbar Vertebrae / Q000187:drug effects / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015675:Osteocalcin / Q000235:genetics; D010012:Osteogenesis / Q000187:drug effects*; D010052:Ovariectomy; D047495:PPAR gamma / Q000235:genetics; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics; D018078:Receptors, Prostaglandin E / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000235:genetics; D058309:Receptors, Prostaglandin E, EP4 Subtype; D013131:Spine / Q000187:drug effects / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology*
C429966:APS-999 Na; D024042:Collagen Type I; D050659:Core Binding Factor Alpha 1 Subunit; D047495:PPAR gamma; D011448:Prostaglandin Antagonists; C545652:Ptger4 protein, rat; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D018078:Receptors, Prostaglandin E; D058309:Receptors, Prostaglandin E, EP4 Subtype; C493717:Runx2 protein, rat; D013438:Sulfhydryl Compounds; D013876:Thiophenes; D016222:Fibroblast Growth Factor 2; D015675:Osteocalcin