Β₁ integrins mediate mechanosensitive signaling pathways in osteocytes

Litzenberger, Julie B.<sup>1,2</sup>; Kim, Jae-Beom<sup>3,4</sup>; Tummala, Padmaja<sup>1,5</sup>; Jacobs, Christopher R.<sup>6</sup>

Affiliations

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

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

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

⁴Caliper Life Sciences, Alameda, CA, USA

⁵MedImmune Vaccines, Mountain View, CA, USA

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

Abstract and keywords

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.

Keywords: Integrin; Mechanotransduction; Osteocyte; Fluid flow; Bone

Links

DOI: 10.1007/s00223-010-9343-6

PubMed: 20213106

WoS: 000276046900006

History

Received: 2009-09-29

Accepted: 2010-02-07

Online: 2010-03-06

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