RRC ID 70304
Author Shimizu T, Fujita N, Tsuji-Tamura K, Kitagawa Y, Fujisawa T, Tamura M, Sato M.
Title Osteocytes as main responders to low-intensity pulsed ultrasound treatment during fracture healing.
Journal Sci Rep
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.
Volume 11(1)
Pages 10298
Published 2021-5-13
DOI 10.1038/s41598-021-89672-9
PII 10.1038/s41598-021-89672-9
PMID 33986415
PMC PMC8119462
MeSH Animals Cell Line Fracture Healing / genetics Fracture Healing / physiology* Mice Osteocytes / metabolism Osteocytes / physiology* Transcription, Genetic Ultrasonic Waves* Zebrafish
IF 3.998
Medaka OK-Cab
Zebrafish RIKEN WT