Study of Osteocyte Behavior by High-Resolution Intravital Imaging Following Photo-Induced Ischemia

Hengfeng Yuan,Betty Kim,Wen Jiang,Yuanxin Chen

doi:10.3390/molecules23112874

Abstract

Ischemic injuries and local hypoxia can result in osteocytes dysfunction and play a key role in the pathogenesis of avascular osteonecrosis. Conventional imaging techniques including magnetic resonance imaging (MRI) and computed tomography (CT) can reveal structural and functional changes within bony anatomy; however, characterization of osteocyte behavioral dynamics in the setting of osteonecrosis at the single cell resolution is limited. Here, we demonstrate an optical approach to study real-time osteocyte functions in vivo. Using nicotinamide adenine dinucleotide (NADH) as a biomarker for metabolic dynamics in osteocytes, we showed that NADH level within osteocytes transiently increase significantly after local ischemia through non-invasive photo-induced thrombosis of afferent arterioles followed by a steady decline. Our study presents a non-invasive optical approach to study osteocyte behavior through the modulation of local environmental conditions. Thus it provides a powerful toolkit to study cellular processes involved in bone pathologies in vivo.

Highlights

Avascular osteonecrosis (AVN), commonly found in the regions of femoral head, is associated with bony cell death
Our current study proposes a novel, all our optical-based approach to the and long-term imaging of necrotic processes occurring in mouse calvaria, goal is to characterize generate and study the hypoxic microenvironment of Performing high deterministic relationships between vascular occlusion, osteocyte death, and changes inresolution intracellular real-time and long-term imaging of necrotic processes occurring in mouse calvaria, our goal is to metabolic demand that contribute to the development of AVN
Complexand andinvolves involves multiple multiple cellular cellular processes studies have proposed ways to artificially induce animalmodels modelsincluding includingpulsed pulseddelivery delivery of studies have proposed ways to artificially induce inin animal of corticosteroids. These methodsmay maycause causeside side effects effects like and corticosteroids. These methods like thinning thinningbones bones and fractures, and it is unclear whether these models represent similar pathophysiology as fractures, and it is unclear whether these models represent similar pathophysiology as AVN

Summary

Introduction

Avascular osteonecrosis (AVN), commonly found in the regions of femoral head, is associated with bony cell death. The decreased oxygen tension causes osteocyte death and eventual collapse of subchondral bones [3,4]. Modern imaging techniques, such as magnetic resonance imaging (MRI), Single-photon emission computerized tomography (SPECT) and positron emission tomography (PET), have been utilized extensively in clinical settings to diagnose AVN [5,6,7,8]. Imaging-based approaches that rely on optical platforms to study the cellular and molecular pathogenesis of AVN, possess unique technical challenges due to the high photon attenuation of calcified bone matrix

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