PUBLICATION
Osteocytes as main responders to low-intensity pulsed ultrasound treatment during fracture healing
- Authors
- Shimizu, T., Fujita, N., Tsuji-Tamura, K., Kitagawa, Y., Fujisawa, T., Tamura, M., Sato, M.
- ID
- ZDB-PUB-210515-5
- Date
- 2021
- Source
- Scientific Reports 11: 10298 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Cell Line
- Fracture Healing/genetics
- Fracture Healing/physiology*
- Mice
- Osteocytes/metabolism
- Osteocytes/physiology*
- Transcription, Genetic
- Ultrasonic Waves*
- Zebrafish
- PubMed
- 33986415 Full text @ Sci. Rep.
Citation
Shimizu, T., Fujita, N., Tsuji-Tamura, K., Kitagawa, Y., Fujisawa, T., Tamura, M., Sato, M. (2021) Osteocytes as main responders to low-intensity pulsed ultrasound treatment during fracture healing. Scientific Reports. 11:10298.
Abstract
Ultrasound stimulation is a type of mechanical stress, and low-intensity pulsed ultrasound (LIPUS) devices have been used clinically to promote fracture healing. However, it remains unclear which skeletal cells, in particular osteocytes or osteoblasts, primarily respond to LIPUS stimulation and how they contribute to fracture healing. To examine this, we utilized medaka, whose bone lacks osteocytes, and zebrafish, whose bone has osteocytes, as in vivo models. Fracture healing was accelerated by ultrasound stimulation in zebrafish, but not in medaka. To examine the molecular events induced by LIPUS stimulation in osteocytes, we performed RNA sequencing of a murine osteocytic cell line exposed to LIPUS. 179 genes reacted to LIPUS stimulation, and functional cluster analysis identified among them several molecular signatures related to immunity, secretion, and transcription. Notably, most of the isolated transcription-related genes were also modulated by LIPUS in vivo in zebrafish. However, expression levels of early growth response protein 1 and 2 (Egr1, 2), JunB, forkhead box Q1 (FoxQ1), and nuclear factor of activated T cells c1 (NFATc1) were not altered by LIPUS in medaka, suggesting that these genes are key transcriptional regulators of LIPUS-dependent fracture healing via osteocytes. We therefore show that bone-embedded osteocytes are necessary for LIPUS-induced promotion of fracture healing via transcriptional control of target genes, which presumably activates neighboring cells involved in fracture healing processes.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping