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β1 Integrins Mediate Mechanosensitive Signaling Pathways in Osteocytes

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Abstract

Integrins are cell-substrate adhesion proteins that initiate intracellular signaling and may serve as mechanosensors in bone. MLO-Y4 cells were stably transfected with a dominant negative form of the β1 integrin subunit (β1DN) containing the transmembrane domain and cytoplasmic tail of β1 integrin. Cells expressing β1DN had reduced vinculin localization to focal contacts but no change in intracellular actin organization. When exposed to oscillatory fluid flow, β1DN cells exhibited a significant reduction in the upregulation of cyclooxygenase-2 gene expression and prostaglandin E2 release. Similarly, the ratio of receptor activator of NF-κB ligand mRNA to osteoprotegerin mRNA decreased significantly after exposure to fluid flow in control cells but not in β1DN cells. Interfering with integrin signaling did not affect mechanically induced intracellular calcium mobilization. These data suggest that integrins may initiate the cellular response of osteocytes to dynamic fluid flow and may serve as mechanosensitive molecules in bone.

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Authors and Affiliations

  1. Department of Veterans Affairs, Bone and Joint Rehabilitation Center, Palo Alto, CA, USA

    Julie B. Litzenberger & Padmaja Tummala

  2. Department of Bioengineering, Stanford University, Stanford, CA, USA

    Julie B. Litzenberger

  3. Department of Stomatology, University of California, Stanford, CA, USA

    Jae-Beom Kim

  4. Caliper Life Sciences, Alameda, CA, USA

    Jae-Beom Kim

  5. MedImmune Vaccines, Mountain View, CA, USA

    Padmaja Tummala

  6. Biomedical Engineering Department, Columbia University, 500 W. 120th St., 351 Engineering Terrace, New York, NY, 10027, USA

    Christopher R. Jacobs

Authors
  1. Julie B. Litzenberger
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  2. Jae-Beom Kim
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  3. Padmaja Tummala
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  4. Christopher R. Jacobs
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Correspondence to Christopher R. Jacobs.

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The authors have stated that they have no conflict of interest.

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Litzenberger, J.B., Kim, JB., Tummala, P. et al. β1 Integrins Mediate Mechanosensitive Signaling Pathways in Osteocytes. Calcif Tissue Int 86, 325–332 (2010). https://doi.org/10.1007/s00223-010-9343-6

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  • DOI: https://doi.org/10.1007/s00223-010-9343-6

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