Mechanosensory responses of osteocytes to physiological forces occur along processes and not cell body and require αvβ3 integrin

Mia M. Thi, Sylvia O. Suadicani, Mitchell B. Schaffler, Sheldon Weinbaum, David C. Spray

Research output: Contribution to journalArticle

62 Scopus citations

Abstract

Osteocytes in the lacunar-canalicular system of the bone are thought to be the cells that sense mechanical loading and transduce mechanical strain into biomechanical responses. The goal of this study was to evaluate the extent to which focal mechanical stimulation of osteocyte cell body and process led to activation of the cells, and determine whether integrin attachments play a role in osteocyte activation. We use a novel Stokesian fluid stimulus probe to hydrodynamically load osteocyte processes vs. cell bodies in murine long bone osteocyte Y4 (MLO-Y4) cells with physiologicallevel forces <10 pN without probe contact, and measured intracellular Ca2+ responses. Our results indicate that osteocyte processes are extremely responsive to piconewton-level mechanical loading, whereas the osteocyte cell body and processes with no local attachment sites are not. Ca2+ signals generated at stimulated sites spread within the processes with average velocity of 5.6 μm/s. Using the near-infrared fluorescence probe IntegriSense 750, we demonstrated that inhibition of αVβ3 integrin attachment sites compromises the response to probe stimulation. Moreover, using apyrase, an extracellular ATP scavenger, we showed that Ca2+ signaling from the osteocyte process to the cell body was greatly diminished, and thus dependent on ATP-mediated autocrine signaling. These findings are consistent with the hypothesis that osteocytes in situ are highly polarized cells, where mechanotransduction occurs at substrate attachment sites along the processes at force levels predicted to occur at integrin attachment sites in vivo. We also demonstrate the essential role of αVβ3 integrin in osteocyte-polarized mechanosensing and mechanotransduction.

Original languageEnglish (US)
Pages (from-to)21012-21017
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number52
DOIs
StatePublished - Dec 24 2013

Keywords

  • Cell process attachment
  • Fluid flow activation
  • Intracellular calcium
  • Purinergic signaling

ASJC Scopus subject areas

  • General

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