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Osteocytes as main responders to low-intensity pulsed ultrasound treatment during fracture healing

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Title: Osteocytes as main responders to low-intensity pulsed ultrasound treatment during fracture healing
Authors: Shimizu, Tatsuya Browse this author
Fujita, Naomasa Browse this author
Tsuji-Tamura, Kiyomi Browse this author →KAKEN DB
Kitagawa, Yoshimasa Browse this author →KAKEN DB
Fujisawa, Toshiaki Browse this author →KAKEN DB
Tamura, Masato Browse this author →KAKEN DB
Sato, Mari Browse this author →KAKEN DB
Issue Date: 13-May-2021
Publisher: Nature Research
Journal Title: Scientific reports
Volume: 11
Issue: 1
Start Page: 10298
Publisher DOI: 10.1038/s41598-021-89672-9
PMID: 33986415
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.
Type: article
Appears in Collections:歯学院・歯学研究院 (Graduate School of Dental Medicine / Faculty of Dental Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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