Anabolic actions of parathyroid hormone during bone growth are dependent on c-fos

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Demiralp B., Chen H., Koh A., Keller E., McCauley L.

ENDOCRINOLOGY, vol.143, no.10, pp.4038-4047, 2002 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 143 Issue: 10
  • Publication Date: 2002
  • Doi Number: 10.1210/en.2002-220221
  • Journal Name: ENDOCRINOLOGY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.4038-4047
  • Hacettepe University Affiliated: Yes


PTH has anabolic and catabolic actions in bone that are not clearly understood. The protooncogene c-fos and other activating protein 1 family members are critical transcriptional mediators in bone, and c-fos is up-regulated by PTH. The purpose of this study was to examine the mechanisms of PTH and the role of c-fos in PTH-mediated anabolic actions in bone. Mice with ablation of c-fos (-/-) and their wild-type (+/+) and heterozygous (+/-) littermates were administered PTH for 17 d. The +/+ mice had increased femoral bone mineral density (BMD), whereas -/- mice had reduced BMD after PTH treatment. PTH increased the ash weight of +/+ and but not -/-, femurs and decreased the calcium content of but not +/+ or +/-, femurs. Histomorphometric analysis showed that PTH increased trabecular bone volume in c-fos +/+, +/- vertebrae, but, in contrast, decreased trabecular bone in -/- vertebrae. Serum calcium levels in +/+ mice were greater than those in -/- mice, and PTH increased calcium in -/- mice. Histologically, PTH resulted in an exacerbation of the already widened growth plate and zone of hypertrophic chondrocytes but not the proliferating zone in -/- mice. PTH also increased calvarial thickness in +/+ mice, but not -/- mice. The c-fos -/- mice had lower bone sialoprotein and osteocalcin (OCN), but unaltered PTH-1 receptor mRNA expression in calvaria, suggesting an alteration in extracellular matrix. Acute PTH injection (8 h) resulted in a decrease in osteocalcin mRNA expression in wild-type, but unaltered expression in -/-, calvaria. These data indicate that c-fos plays a critical role in the anabolic actions of PTH during endochondral bone growth.