Potential role for a specialized β3 integrin-based structure on osteocyte processes in bone mechanosensation

Pamela Cabahug-Zuckerman, Randy F. Stout, Robert J. Majeska, Mia M. Thi, David C. Spray, Sheldon Weinbaum, Mitchell B. Schaffler

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Osteocyte processes are an order of magnitude more sensitive to mechanical loading than their cell bodies. The mechanisms underlying this remarkable mechanosensitivity are not clear, but may be related to the infrequent αVβ3 integrin sites where the osteocyte cell processes attach to canalicular walls. These sites develop dramatically elevated strains during load-induced fluid flow in the lacunar-canalicular system and were recently shown to be primary sites for osteocyte-like MLO-Y4 cell mechanotransduction. These αVβ3 integrin sites lack typical integrin transduction mechanisms. Rather, stimulation at these sites alters Ca2+ signaling, ATP release and membrane potential. In the current studies, we tested the hypothesis that in authentic osteocytes in situ, key membrane proteins implicated in osteocyte mechanotransduction are preferentially localized at or near to β3 integrin-foci. We analyzed these spatial relationships in mouse bone osteocytes using immunohistochemistry combined with Structured Illumination Super Resolution Microscopy, a method that permits structural resolution at near electron microscopy levels in tissue sections. We discovered that the purinergic channel pannexin1, the ATP-gated purinergic receptor P2×7R and the low voltage transiently opened T-type calcium channel CaV3.2-1 all reside in close proximity to β3 integrin attachment foci on osteocyte processes, suggesting a specialized mechanotransduction complex at these sites. We further confirmed this observation on isolated osteocytes in culture using STochasitc Optical Resonance Microscopy. These findings identify a possible structural basis for the unique mechanosensation and transduction capabilities of the osteocyte process.

Original languageEnglish (US)
JournalJournal of Orthopaedic Research
DOIs
StateAccepted/In press - Jan 1 2017

Fingerprint

Osteocytes
Integrins
Bone and Bones
Microscopy
Adenosine Triphosphate
T-Type Calcium Channels
Purinergic Receptors
Lighting
Membrane Potentials
Electron Microscopy
Membrane Proteins
Immunohistochemistry

Keywords

  • Bone
  • Bone biology
  • Bone osteocytes and mechanobiology

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

Cite this

Potential role for a specialized β3 integrin-based structure on osteocyte processes in bone mechanosensation. / Cabahug-Zuckerman, Pamela; Stout, Randy F.; Majeska, Robert J.; Thi, Mia M.; Spray, David C.; Weinbaum, Sheldon; Schaffler, Mitchell B.

In: Journal of Orthopaedic Research, 01.01.2017.

Research output: Contribution to journalArticle

Cabahug-Zuckerman, Pamela ; Stout, Randy F. ; Majeska, Robert J. ; Thi, Mia M. ; Spray, David C. ; Weinbaum, Sheldon ; Schaffler, Mitchell B. / Potential role for a specialized β3 integrin-based structure on osteocyte processes in bone mechanosensation. In: Journal of Orthopaedic Research. 2017.
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