Mechanically driven In vivo Osteocyte Ca2+ Signaling: Aging and Pharmacologic Effects
type: CreativeWork
description: Bone’s ability to respond and adapt to mechanical loading declines significantly with age which is a major contributor to bone fragility. It is widely accepted that osteocytes are the key cells responsible for orchestrating the development of the “ideal” skeleton. This ability is attributed to osteocyte’s role as the primary mechanosensing cell that is responsible for maintaining the skeleton’s integrity throughout life. Recent work from our laboratory has shed light into how osteocytes respond to mechanical loading in vivo. The breakthrough approaches that enabled these discoveries were development of: (1) the first ever reporter mouse model with a genetically encoded calcium (Ca2+) indicator (GECI) targeted to osteocytes to allow measurement of osteocyte Ca2+ responses to loading in vivo and (2) novel in vivo bone loading-imaging approaches that allow real-time visualization of osteocyte responses. Using these approaches, this study established that populations of osteocytes in vivo numerically encode bone load magnitude and loading frequency information, with increasing strain levels recruiting more Ca2+ responding osteocytes in healthy young adult bone following a well-defined response curve. Building upon this insight will be the focus of this dissertation. In this dissertation, Chapter 1 provides critical background information on the current understanding of osteocyte mechanotransduction and establishes rationale for subsequent work. Chapter 2 discusses the development and characterization of a novel mouse strain that is capable of producing GCaMP signal throughout its lifespan. We used a tamoxifen-inducible GCaMP reporter mouse that only expressed GCaMP signal when needed. This tamoxifen-inducible mouse has been used in other bone research studies in mice up to 18 months of age. In Chapter 3, we compared the in vivo osteocyte Ca2+ signaling responses to controlled mechanical loading in both male and female young, middle aged, late middle age, and aged adult …
abstract: Bone’s ability to respond and adapt to mechanical loading declines significantly with age which is a major contributor to bone fragility. It is widely accepted that osteocytes are the key cells responsible for orchestrating the development of the “ideal” skeleton. This ability is attributed to osteocyte’s role as the primary mechanosensing cell that is responsible for maintaining the skeleton’s integrity throughout life. Recent work from our laboratory has shed light into how osteocytes respond to mechanical loading in vivo. The breakthrough approaches that enabled these discoveries were development of: (1) the first ever reporter mouse model with a genetically encoded calcium (Ca2+) indicator (GECI) targeted to osteocytes to allow measurement of osteocyte Ca2+ responses to loading in vivo and (2) novel in vivo bone loading-imaging approaches that allow real-time visualization of osteocyte responses. Using these approaches, this study established that populations of osteocytes in vivo numerically encode bone load magnitude and loading frequency information, with increasing strain levels recruiting more Ca2+ responding osteocytes in healthy young adult bone following a well-defined response curve. Building upon this insight will be the focus of this dissertation. In this dissertation, Chapter 1 provides critical background information on the current understanding of osteocyte mechanotransduction and establishes rationale for subsequent work. Chapter 2 discusses the development and characterization of a novel mouse strain that is capable of producing GCaMP signal throughout its lifespan. We used a tamoxifen-inducible GCaMP reporter mouse that only expressed GCaMP signal when needed. This tamoxifen-inducible mouse has been used in other bone research studies in mice up to 18 months of age. In Chapter 3, we compared the in vivo osteocyte Ca2+ signaling responses to controlled mechanical loading in both male and female young, middle aged, late middle age, and aged adult …
author: Padgett, James
keywords: bone, mechanobiology, ion channels, aging, osteocytes, Biological Engineering, Biomechanics and Biotransport, Medical Cell Biology
date published: 2023-01-01T08:00:00Z
date modified: 2026-07-24T01:58:07Z
provider: City University of New York - City College
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: City University of New York - City College