Tacrolimus, FK506, promotes bone formation in bone defect mouse model.

Autor: Nishida S; Department of Pharmacology, Graduate School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo, 142-8555, Japan; Department of Medical and Dental Cooperative Dentistry, Graduate School of Dentistry, Showa University, 2-1-1 Kitasenzoku, Ota, Tokyo, 145-8515, Japan; Pharmacological Research Center, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo, 142-8555, Japan., Azetsu Y; Department of Pharmacology, Graduate School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo, 142-8555, Japan; Pharmacological Research Center, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo, 142-8555, Japan., Chatani M; Department of Pharmacology, Graduate School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo, 142-8555, Japan; Pharmacological Research Center, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo, 142-8555, Japan., Karakawa A; Department of Pharmacology, Graduate School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo, 142-8555, Japan; Pharmacological Research Center, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo, 142-8555, Japan., Otake K; Department of Pharmacology, Graduate School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo, 142-8555, Japan; Pharmacological Research Center, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo, 142-8555, Japan; Department of Endodontology, Graduate School of Dentistry, Showa University, 2-1-1 Kitasenzoku, Ota, Tokyo, 145-8515, Japan., Sugiki H; Department of Pharmacology, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo, 142-8555, Japan., Sakai N; Department of Dental Education, Showa University School of Dentistry, 1-5-8 Hatanodai, Shinagawa, Tokyo, 142-8555, Japan., Maruoka Y; Totsuka Kyoritsu Daini Hospital, 579-1 Totsuka, Yokohama, Kanagawa, 244-0817, Japan., Myers M; Department of Medical and Dental Cooperative Dentistry, School of Dentistry, Showa University, 2-1-1 Kitasenzoku, Ota, Tokyo, 145-8515, Japan., Takami M; Department of Pharmacology, Graduate School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo, 142-8555, Japan; Pharmacological Research Center, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo, 142-8555, Japan. Electronic address: takami@dent.showa-u.ac.jp.
Jazyk: angličtina
Zdroj: Journal of oral biosciences [J Oral Biosci] 2024 Jun; Vol. 66 (2), pp. 391-402. Date of Electronic Publication: 2024 Feb 14.
DOI: 10.1016/j.job.2024.02.003
Abstrakt: Objectives: Some studies have reported that tacrolimus (FK506), an immunosuppressant, may have positive effects on bone formation. However, the precise effects of FK506 on bone repair or osteoblasts remain inadequately elucidated, and limited research has explored the outcomes of its use in an in vivo mouse model. This study aims to examine the effects of FK506 on bone repair and osteoblast functions using bone defect and BMP-2-induced ectopic ossification mouse models, as well as cultured primary mouse osteoblasts treated with FK506.
Methods: We established mouse models of femur bone defect and BMP-2-induced ectopic ossification to evaluate the effect of FK506 on new bone formation, respectively. Additionally, primary mouse osteoblasts were cultured with FK506 and examined for gene expressions related to osteoblast differentiation.
Results: While FK506 promoted the repair of bone defect areas in the femur of the bone defect mouse model, it also led to widespread abnormal bone formation outside the intended area. Additionally, following the implantation of a collagen sponge containing BMP-2 into mouse muscle tissue, FK506 was found to promote ectopic ossification and enhance BMP-2-induced osteoblast differentiation in vitro. Our findings also revealed that FK506 increased the number of immature osteoblasts in the absence of BMP-2 without affecting osteoblast differentiation. Furthermore, direct effects were observed, reducing the ability of osteoblasts to support osteoclastogenesis.
Conclusions: These results indicate that FK506 increases new bone formation during bone repair and influences the proliferation of immature osteoblasts, as well as osteoblast-supported osteoclastogenesis.
Competing Interests: Declaration of competing interest None of the authors have conflicts of interest to declare regarding the contents of this paper.
(Copyright © 2024 Japanese Association for Oral Biology. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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