Osteoblast Development in Bone Loss Due to Skeletal Unloading

  • Akinori Sakai
  • Toshitaka Nakamura


Introduction: The aim of this study was to clarify signal transduction of osteoblast development in bone loss due to skeletal unloading. We have focused on the p53 gene related to apoptosis and platelet endothelial cell adhesion molecule-1 (PECAM-1) related to osteoblast differentiation.

Methods: We used tibial samples of tail-suspended mice. Histomorphometric analyses were done at the secondary spongiosa of the proximal tibia. Bone formation was evaluated with fluorescence double labeling with calcein and bone resorption with tartrate-resistant acid phosphatase staining. Cell culture study was done using tibial bone marrow cells and cell lines. Alkaline phosphatase (ALP)-positive colony-forming units-fibroblastic (CFU-f) was measured for the evaluation of osteogenic potential.

Results: Unloading rapidly reduced trabecular bone volume, bone formation rate, and ALP-positive CFU-f in 7 days. However, disruption of the p53 gene alleviated these reductions. The expression of PECAM-1 in bone marrow cells decreased by unloading and recovered following reloading. Addition of anti-PECAM-1 antibody into the culture medium suppressed ALP-positive CFU-f formation. ALP produced by osteoblasts is enhanced in combination with an endothelial cell line with PECAM-1 expression, but not an endothelial cell line without PECAM-1 expression. Anti-PECAM-1 antibody dose-dependently reduced the increase in ALP production of osteoblasts cocultured with endothelial cell line with PECAM-1 expression.

Conclusion: Skeletal unloading reduced osteoblast proliferation and differentiation through at least two independent pathways in bone marrow cells: apoptotic signal through the p53 gene and decreased osteogenic potential related to reduction of PECAM-1 expression.


Bone Marrow Cell Fluid Shear Stress Endothelial Cell Line Trabecular Bone Volume Osteoblast Development 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Springer 2011

Authors and Affiliations

  1. 1.Department of Orthopaedic Surgery, School of MedicineUniversity of Occupational and Environmental HealthYahatanishi-kuJapan
  2. 2.Department of Orthopaedic Surgery, School of MedicineUniversity of Occupational and Environmental HealthYahatanishi-kuJapan

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