High resolution imaging of the osteogenic and angiogenic interface at the site of murine cranial bone defect repair via multiphoton microscopy
- University of Rochester, United States
- Shanghai Institutes for Biological Sciences, China
Abstract
The spatiotemporal blood vessel formation and specification at the osteogenic and angiogenic interface of murine cranial bone defect repair were examined utilizing a high-resolution multiphoton-based imaging platform in conjunction with advanced optical techniques that allow interrogation of the oxygen microenvironment and cellular energy metabolism in living animals. Our study demonstrates the dynamic changes of vessel types, i.e. arterial, venous and capillary vessel networks at the superior and dura periosteum of cranial bone defect, suggesting a differential coupling of the vessel type with osteoblast expansion and bone tissue deposition/remodeling during repair. Employing transgenic reporter mouse models that label distinct types of vessels at the site of repair, we further show that oxygen distributions in capillary vessels at the healing site are heterogeneous as well as time and location-dependent. The endothelial cells coupling to osteoblasts prefer glycolysis and are less sensitive to microenvironmental oxygen changes than osteoblasts. In comparison, osteoblasts utilize relatively more OxPhos and potentially consume more oxygen at the site of repair. Taken together, our study highlights the dynamics and functional significance of blood vessel types at the site of defect repair, opening up opportunities for further delineating the oxygen and metabolic microenvironment at the interface of bone tissue regeneration.
Data availability
Data Availability: All data source files used to generate each figure are provided as Source data.
Article and author information
Author details
Funding
National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR067859,R21AR076056,P30AR069655)
- Xinping Zhang
National Institute of Dental and Craniofacial Research (R01DE019902,R21DE026256,R01DE029790)
- Xinping Zhang
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All in vivo experiments were performed using adult 8 to 12-week-old animals housed in pathogen-free, temperature and humidity-controlled facilities with a 12-hour day-night cycle in the vivarium at the University of Rochester Medical Center. All cages contained wood shavings, bedding and a cardboard tube for environmental enrichment. All experimental procedures were reviewed and approved by the University Committee on Animal Resources (Protocol UCAR2009-060). General anesthesia, and analgesia procedures were performed based on the mouse formulary provided by the University Committee on Animal Resources at the University of Rochester. The animals' health status was monitored throughout the experiments by experienced veterinarians according to the Guide for the Care and Use of Laboratory Animals outlined by the National Institute of Health.
Copyright
© 2022, Schilling et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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High resolution imaging of the osteogenic and angiogenic interface at the site of murine cranial bone defect repair via multiphoton microscopy
eLife 11:e83146.
https://doi.org/10.7554/eLife.83146
