Abstract

A primary goal of bone research is to understand the mechanism(s) by which mechanical forces dictate the cellular and metabolic activities of osteoblasts, the bone-forming cells. Several studies indicate that osteblastic cells respond to physical loading by transducing signals that alter gene expression patterns. Accumulated data have documented the fundamental role of the osteoblast-specific transcription factor Cbfa1 (core-binding factor) in osteoblast differentiation and function. Here, we demonstrate that low level mechanical deformation (stretching) of human osteoblastic cells directly up-regulates the expression and DNA binding activity of Cbfa1. This effect seems to be fine tuned by stretch-triggered induction of distinct mitogen-activated protein kinase cascades. Our novel finding that activated extracellular signal-regulated kinase mitogen-activated protein kinase physically interacts and phosphorylates endogenous Cbfa1 in vivo (ultimately potentiating this transcription factor) provides a molecular link between mechanostressing and stimulation of osteoblast differentiation. Elucidation of the specific modifiers and cofactors that operate in this mechanotranscription circuitry will contribute to a better understanding of mechanical load-induced bone formation which may set the basis for nonpharmacological intervention in bone loss pathologies.

Highlights

  • Mechanical stress has been long recognized to be an important regulatory factor in bone homeostasis and a determinant of skeletal morphology during development and in postnatal life [1]

  • Cbfa1 binds to the osteoblast-specific cis-acting element 2 (OSE2)1 [3], which is found in the promoter regions of all the major osteoblast-specific genes and controls their expression [2, 4, 5]

  • Mechanical Stretch Induces Cbfa1 Expression in human periodontal ligament (hPDL) Osteoblastic Cells—It is well established that hPDL cells bear an osteoblastic potential (20 –22)

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Summary

Introduction

Mechanical stress has been long recognized to be an important regulatory factor in bone homeostasis and a determinant of skeletal morphology during development and in postnatal life [1]. We demonstrate that low level mechanical deformation (stretching) of human osteoblastic cells directly up-regulates the expression and DNA binding activity of Cbfa1.

Results
Conclusion

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