Osteopenia, decreased bone formation and impaired osteoblast development in Sox4 heterozygous mice

Lise Sofie Haug Nissen-Meyer, Run Jemtland, Vigdis T. Gautvik, Mona E. Pedersen, Rita Paro, Dario Fortunati, Dominique Pierroz, Vincent A. Stadelmann, Sjur Reppe, Finn P. Reinholt, Andrea Del Fattore, Nadia Rucci, Anna Teti, Serge Ferrari, Kaare M. Gautvik

Research output: Contribution to journalArticle

Abstract

The transcription factor Sox4 is vital for fetal development, as Sox4-/ - homozygotes die in utero. Sox4 mRNA is expressed in the early embryonic growth plate and is regulated by parathyroid hormone, but its function in bone modeling/remodeling is unknown. We report that Sox4+/ - mice exhibit significantly lower bone mass (by dual-energy X-ray absorptiometry) from an early age, and fail to obtain the peak bone mass of wild-type (WT) animals. Microcomputed tomography (μCT), histomorphometry and biomechanical testing of Sox4+/- bones show reduced trabecular and cortical thickness, growth plate width, ultimate force and stiffness compared with WT. Bone formation rate (BFR) in 3-month-old Sox4+/- mice is 64% lower than in WT. Primary calvarial osteoblasts from Sox4+/- mice demonstrate markedly inhibited proliferation, differentiation and mineralization. In these cultures, osterix (Osx) and osteocalcm (OCN) mRNA expression was reduced, whereas Runx2 mRNA was unaffected. No functional defects were found in osteoclasts. Silencing of Sox4 by siRNA in WT osteoblasts: replicated the defects observed in Sox4+/- cells. We demonstrate inhibited formation and altered microarchitecture of bone in Sox4+/- mice versus WT, without apparent defects in bone resorption. Our results implicate the transcription factor Sox4 in regulation of bone formation, by acting upstream of Osx and independent of Runx2.

Original languageEnglish
Pages (from-to)2785-2795
Number of pages11
JournalJournal of Cell Science
Volume120
Issue number16
DOIs
Publication statusPublished - Aug 15 2007

Keywords

  • Bone biomechanics
  • Bone density
  • Bone formation rate
  • Osteoblast cultures
  • Osteoblast function
  • Sox4

ASJC Scopus subject areas

  • Cell Biology

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  • Cite this

    Nissen-Meyer, L. S. H., Jemtland, R., Gautvik, V. T., Pedersen, M. E., Paro, R., Fortunati, D., Pierroz, D., Stadelmann, V. A., Reppe, S., Reinholt, F. P., Del Fattore, A., Rucci, N., Teti, A., Ferrari, S., & Gautvik, K. M. (2007). Osteopenia, decreased bone formation and impaired osteoblast development in Sox4 heterozygous mice. Journal of Cell Science, 120(16), 2785-2795. https://doi.org/10.1242/jcs.003855