Calcified Tissue International

, Volume 90, Issue 2, pp 76–89 | Cite as

Ectopic Expression of SOX9 in Osteoblasts Alters Bone Mechanical Properties

  • Bojian Liang
  • Meghan M. Cotter
  • Dongxing Chen
  • Christopher J. Hernandez
  • Guang Zhou
Original Research


Osteoporosis is a common skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. We previously demonstrated that Col1a1-SOX9 transgenic (TG) mice, in which SOX9 specifically expresses in osteoblasts driven by a 2.3-kb Col1a1 promoter, display osteopenia during the early postnatal stage. In this study, to further analyze the osteopenia phenotype and especially the effect of the osteoblast-specific expression of SOX9 on bone mechanical properties, we performed bone geometry and mechanical property analysis of long bones from Col1a1-SOX9 TG mice and wild-type littermates (WT) at different time points. Interestingly, after body weight adjustment, TG mice had similar whole-bone strength as WT mice but significantly thinner cortical bone, lower elastic modulus, and higher moment of inertia. Thus, osteoblast-specific SOX9 expression results in altered bone structure and material properties. Furthermore, the expression levels of Pcna, Col1a1, osteocalcin, and the Opg/Rankl ratio in TG mice were significantly lower until 4 months of age compared with WT mice, suggesting that TG mice have dysregulated bone homeostasis. Finally, bone marrow stromal cells (MSCs) isolated from TG mice display enhanced adipocyte differentiation and decreased osteoblast differentiation in vitro, suggesting that osteoblast-specific expression of SOX9 can lead to altered mesenchymal stem cell differentiation potentials. In conclusion, our study implies that SOX9 activity has to be tightly regulated in the adult skeleton to ensure optimal bone quality.


SOX9 RUNX2 Osteoporosis Bone mechanical property Marrow stromal cell 



This work was supported by NIH grant DE15139 and a Case start-up fund (G. Z.) as well as fellowship support from the Department of Anatomy, Case Western Reserve University (M. M. C.). We thank Chiderah Okoye and Justin Daggett for assistance with image analysis, Teresa Pizzuto for expert histology work, and Dr. David Rowe for 2.3 Col1a1-GFP mice. We also thank Valerie Schmedlen for editorial assistance and Dr. Shunichi Murakami for critical reading of the manuscript.

Supplementary material

223_2011_9550_MOESM1_ESM.pdf (28 kb)
Supplementary material 1 (PDF 21 kb)


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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Bojian Liang
    • 1
    • 6
  • Meghan M. Cotter
    • 2
  • Dongxing Chen
    • 1
  • Christopher J. Hernandez
    • 3
  • Guang Zhou
    • 4
    • 5
    • 7
  1. 1.Department of OrthopaedicsCase Western Reserve UniversityClevelandUSA
  2. 2.Department of AnatomyCase Western Reserve UniversityClevelandUSA
  3. 3.Sibley School of Mechanical and Aerospace EngineeringCornell UniversityIthacaUSA
  4. 4.Department of GeneticsCase Western Reserve UniversityClevelandUSA
  5. 5.Case Comprehensive Cancer CenterCase Western Reserve UniversityClevelandUSA
  6. 6.Department of OrthopaedicsChina-Japan Union Hospital, Jilin UniversityChangchunPeople’s Republic of China
  7. 7.Department of OrthopaedicsCase Western Reserve UniversityClevelandUSA

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