# Structural, Molecular and Functional Specialization in Osteocyte Mechanosensing

> **NIH NIH R01** · CITY COLLEGE OF NEW YORK · 2021 · $615,547

## Abstract

ABSTRACT
Bone adapts its structure to mechanical loading. This adaption is essential for growing the right
skeleton and maintaining its integrity throughout life. Osteocytes are the cells responsible for
sensing and coordinating response to mechanical load. Key recent discoveries reported by our
group during the last several years established that osteocyte cell processes function as unique
mechanosensory elements. Processes are >10-fold more sensitive to mechanical stimuli than
osteocyte cell bodies. Moreover, this triggering of Ca2+ signaling from cell processes occurs
through a unique complex of aVb3 integrins, membrane channels and receptors, that occur at
attachment points to the canalicular walls, and which we call the “Osteocyte mechanosome.”
This proposal is based on the global hypothesis that a novel structure localized on osteocyte
processes, the osteocyte mechanosome, detects and transduces mechanical signals. To date,
we have identified four key osteocyte mechanosome components: αVβ3 integrin, pannexin1,
P2X7 receptor (P2X7R) and the CaV3.2 T-type calcium channel. Our multidisciplinary team will
test this hypothesis by multiple approaches in each of three aims. In Aim 1 we will combine
biochemical techniques (co-immunoprecipitation, surface plasmon resonance) and imaging
modalities (FRAP, FRET and STORM super-resolution microscopy) to define comprehensively
the structural and dynamic properties of this heretofore unknown transduction complex, the
osteocyte mechanosome in osteocytic cells in vitro. In Aim 2 we test how pharmacological and
genetic alteration of individual mechanosome components alters upstream (Ca2+) and
downstream (to bone) signaling in osteocytic cells in vitro. In Aim 3, we will combine our novel
OtGP3 osteocyte Ca2+ reporter mice-in vivo loading/imaging system with pharmacological
manipulations to confirm effects of key mechanosome components (as identified in Aims 1 and
2) on osteocyte Ca2+ response and on downstream signaling. We will also use this approach to
answer the fundamental question of whether osteocyte Ca2+ responses to mechanical loading
altered by loss of constitutive sex hormones (estrogen/androgen) or by anabolic PTH.

## Key facts

- **NIH application ID:** 10138993
- **Project number:** 5R01AR070547-04
- **Recipient organization:** CITY COLLEGE OF NEW YORK
- **Principal Investigator:** MITCHELL B SCHAFFLER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $615,547
- **Award type:** 5
- **Project period:** 2018-07-11 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10138993

## Citation

> US National Institutes of Health, RePORTER application 10138993, Structural, Molecular and Functional Specialization in Osteocyte Mechanosensing (5R01AR070547-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10138993. Licensed CC0.

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