The bone-specific transcriptional regulator Cbfa1 is a target of mechanical signals in osteoblastic cells

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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.

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Ziros, P. G., Gil, A. P. R., Georgakopoulos, T., Habeos, I., Kletsas, D., Basdra, E. K., & Papavassiliou, A. G. (2002). The bone-specific transcriptional regulator Cbfa1 is a target of mechanical signals in osteoblastic cells. Journal of Biological Chemistry, 277(26), 23934–23941. https://doi.org/10.1074/jbc.M109881200

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