Forkhead box O transcription factors in chondrocytes regulate endochondral bone formation

G. Eelen, L. Verlinden, C. Maes, I. Beullens, C. Gysemans, J. H. Paik, R. A. DePinho, R. Bouillon, G. Carmeliet, A. Verstuyf

Research output: Contribution to journalReview articlepeer-review

19 Scopus citations

Abstract

The differentiation of embryonic mesenchymal cells into chondrocytes and the subsequent formation of a cartilaginous scaffold that enables the formation of long bones are hallmarks of endochondral ossification. During this process, chondrocytes undergo a remarkable sequence of events involving proliferation, differentiation, hypertrophy and eventually apoptosis. Forkhead Box O (FoxO) transcription factors (TFs) are well-known regulators of such cellular processes. Although FoxO3a was previously shown to be regulated by 1,25-dihydroxyvitamin D3 in osteoblasts, a possible role for this family of TFs in chondrocytes during endochondral ossification remains largely unstudied. By crossing Collagen2-Cre mice with FoxO1lox/lox;FoxO3alox/lox;FoxO4lox/lox mice, we generated mice in which the three main FoxO isoforms were deleted in growth plate chondrocytes (chondrocyte triple knock-out; CTKO). Intriguingly, CTKO neonates showed a distinct elongation of the hypertrophic zone of the growth plate. CTKO mice had increased overall body and tail length at eight weeks of age and suffered from severe skeletal deformities at older ages. CTKO chondrocytes displayed decreased expression of genes involved in redox homeostasis. These observations illustrate the importance of FoxO signaling in chondrocytes during endochondral ossification.

Original languageEnglish (US)
Pages (from-to)337-343
Number of pages7
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume164
DOIs
StatePublished - Nov 1 2016

Keywords

  • Chondrocyte
  • Forkhead Box O
  • Growth plate
  • Hypertrophic
  • Redox homeostasis

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

Fingerprint

Dive into the research topics of 'Forkhead box O transcription factors in chondrocytes regulate endochondral bone formation'. Together they form a unique fingerprint.

Cite this