Impaired osteoclast formation in bone marrow cultures of Fgf2 null mice in response to parathyroid hormone

Yosuke Okada, Aldemar Montero, Xuxia Zhang, Takanori Sobue, Joseph Lorenzo, Thomas C Doetschman, J. Douglas Coffin, Marja M. Hurley

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Fibroblast growth factor (FGF)-2 and parathyroid hormone (PTH) are potent inducers of osteoclast (OCL) formation, and PTH increases FGF-2 mRNA and protein expression in osteoblasts. To elucidate the role of endogenous FGF-2 in PTH responses, we examined PTH-induced OCL formation in bone marrow cultures from wild type and mice with a disruption of the Fgf2 gene. FGF-2-induced OCL formation was similar in marrow culture from both genotypes. In contrast, PTH-stimulated OCL formation in bone marrow cultures or co-cultures of osteoblast-spleen cells from Fgf2-/- mice was significantly impaired. PTH increased RANKL mRNA expression in osteoblasts cultures from both genotypes. After 6 days of treatment, osteoprotegerin protein in cell supernatants was 40-fold higher in vehicle-treated and 30-fold higher in PTH-treated co-cultures of osteoblast and spleen cells from Fgf2-/- mice compared with Fgf2+/+ mice. However, a neutralizing antibody to osteoprotegerin did not rescue reduced OCL formation in response to PTH. Injection of PTH caused hypercalcemia in Fgf2+/+ but not Fgf2-/- mice. We conclude that PTH stimulates OCL formation and bone resorption in mice in part by endogenous FGF-2 synthesis by osteoblasts. Because RANKL- and interleukin-11-induced OCL formation was also reduced in bone marrow cultures from Fgf2-/- mice, we further conclude that endogenous FGF-2 is necessary for maximal OCL formation by multiple bone resorbing factors.

Original languageEnglish (US)
Pages (from-to)21258-21266
Number of pages9
JournalJournal of Biological Chemistry
Volume278
Issue number23
DOIs
StatePublished - Jun 6 2003
Externally publishedYes

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Osteoclasts
Parathyroid Hormone
Bone
Bone Marrow
Fibroblast Growth Factor 2
Osteoblasts
Cell culture
Osteoprotegerin
Coculture Techniques
Spleen
Genotype
Interleukin-11
Messenger RNA
Hypercalcemia
Bone Resorption
Neutralizing Antibodies
Osteogenesis
Proteins
Genes
Injections

ASJC Scopus subject areas

  • Biochemistry

Cite this

Impaired osteoclast formation in bone marrow cultures of Fgf2 null mice in response to parathyroid hormone. / Okada, Yosuke; Montero, Aldemar; Zhang, Xuxia; Sobue, Takanori; Lorenzo, Joseph; Doetschman, Thomas C; Coffin, J. Douglas; Hurley, Marja M.

In: Journal of Biological Chemistry, Vol. 278, No. 23, 06.06.2003, p. 21258-21266.

Research output: Contribution to journalArticle

Okada, Yosuke ; Montero, Aldemar ; Zhang, Xuxia ; Sobue, Takanori ; Lorenzo, Joseph ; Doetschman, Thomas C ; Coffin, J. Douglas ; Hurley, Marja M. / Impaired osteoclast formation in bone marrow cultures of Fgf2 null mice in response to parathyroid hormone. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 23. pp. 21258-21266.
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