Osteopenia, decreased bone formation and impaired osteoblast development in Sox4 heterozygous mice
| Autor: | Mona Elisabeth Pedersen, Andrea Del Fattore, Nadia Rucci, Sjur Reppe, Dominique D. Pierroz, Dario Fortunati, Rita Paro, Serge Ferrari, Kaare M. Gautvik, Anna Teti, Rune Jemtland, Vigdis T. Gautvik, Vincent A. Stadelmann, Finn P. Reinholt, Lise Sofie H. Nissen-Meyer |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Male
Peak bone mass Heterozygote medicine.medical_specialty Bone density Osteoclasts Parathyroid hormone Bone Marrow Cells Core Binding Factor Alpha 1 Subunit Haploidy Biology Bone resorption SOXC Transcription Factors Mice Bone Density Osteogenesis Internal medicine medicine Animals RNA Small Interfering Cells Cultured Osteoblasts High Mobility Group Proteins Cell Differentiation Osteoblast Cell Biology medicine.disease RUNX2 Osteopenia Bone Diseases Metabolic medicine.anatomical_structure Endocrinology Gene Expression Regulation Parathyroid Hormone Trans-Activators Osteocalcin biology.protein Calcium Female Morbidity Tomography X-Ray Computed Biomarkers |
| Zdroj: | Journal of Cell Science. 120:2785-2795 |
| ISSN: | 1477-9137 0021-9533 |
| Popis: | 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 osteocalcin (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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|