Forkhead box O transcription factors in chondrocytes regulate endochondral bone formation.

TitleForkhead box O transcription factors in chondrocytes regulate endochondral bone formation.
Publication TypeJournal Article
Year of Publication2016
AuthorsEelen G, Verlinden L, Maes C, Beullens I, Gysemans C, Paik J-H, DePinho RA, Bouillon R, Carmeliet G, Verstuyf A
JournalJ Steroid Biochem Mol Biol
Date Published2016 11
KeywordsAnimals, Bone and Bones, Cell Cycle Proteins, Cell Differentiation, Cell Proliferation, Chondrocytes, Collagen Type II, Crosses, Genetic, Female, Forkhead Box Protein O1, Forkhead Box Protein O3, Forkhead Transcription Factors, Gene Expression Profiling, Gene Expression Regulation, Developmental, Integrases, Male, Mesenchymal Stem Cells, Mice, Mice, Transgenic, Osteogenesis, Oxidoreductases, Primary Cell Culture, Signal Transduction

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 D in osteoblasts, a possible role for this family of TFs in chondrocytes during endochondral ossification remains largely unstudied. By crossing Collagen2-Cre mice with FoxO1;FoxO3a;FoxO4 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.

Alternate JournalJ Steroid Biochem Mol Biol
PubMed ID26232637
Related Faculty: 
Ji-Hye Paik, Ph.D.

Pathology & Laboratory Medicine 1300 York Avenue New York, NY 10065 Phone: (212) 746-6464
Surgical Pathology: (212) 746-2700