A novel macrolide–Del-1 axis to regenerate bone in old age

Kridtapat Sirisereephap; Hikaru Tamura; Jong-Hyung Lim; Meircurius Dwi Condro Surboyo; Toshihito Isono; Takumi Hiyoshi; Andrea L. Rosenkranz; Yurie Sato-Yamada; Hisanori Domon; Akari Ikeda; Tomoyasu Hirose; Toshiaki Sunazuka; Nagako Yoshiba; Hiroyuki Okada; Yutaka Terao; Takeyasu Maeda; Koichi Tabeta; Triantafyllos Chavakis; George Hajishengallis; Tomoki Maekawa

iScience (Feb 2024)

A novel macrolide–Del-1 axis to regenerate bone in old age

Kridtapat Sirisereephap,
Hikaru Tamura,
Jong-Hyung Lim,
Meircurius Dwi Condro Surboyo,
Toshihito Isono,
Takumi Hiyoshi,
Andrea L. Rosenkranz,
Yurie Sato-Yamada,
Hisanori Domon,
Akari Ikeda,
Tomoyasu Hirose,
Toshiaki Sunazuka,
Nagako Yoshiba,
Hiroyuki Okada,
Yutaka Terao,
Takeyasu Maeda,
Koichi Tabeta,
Triantafyllos Chavakis,
George Hajishengallis,
Tomoki Maekawa

Affiliations

Kridtapat Sirisereephap: Division of Periodontology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, Japan; Center for Advanced Oral Science, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, Japan; Faculty of Dentistry, Chulalongkorn University, Bangkok 10330, Thailand
Hikaru Tamura: Center for Advanced Oral Science, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, Japan
Jong-Hyung Lim: Department of Basic and Translational Sciences, Laboratory of Innate Immunity and Inflammation, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Meircurius Dwi Condro Surboyo: Center for Advanced Oral Science, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, Japan; Faculty of Dentistry, Universitas Airlangga, Surabaya 60132, Indonesia
Toshihito Isono: Division of Microbiology and Infectious Diseases, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, Japan
Takumi Hiyoshi: Center for Advanced Oral Science, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, Japan
Andrea L. Rosenkranz: Center for Advanced Oral Science, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, Japan
Yurie Sato-Yamada: Center for Advanced Oral Science, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, Japan
Hisanori Domon: Division of Microbiology and Infectious Diseases, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, Japan
Akari Ikeda: Ōmura Satoshi Memorial Institute, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan; Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan
Tomoyasu Hirose: Ōmura Satoshi Memorial Institute, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan; Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan
Toshiaki Sunazuka: Ōmura Satoshi Memorial Institute, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan; Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan
Nagako Yoshiba: Division of Cariology, Operative Dentistry and Endodontics, Department of Oral Health Science, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, Japan
Hiroyuki Okada: Laboratory of Clinical Biotechnology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
Yutaka Terao: Division of Microbiology and Infectious Diseases, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, Japan
Takeyasu Maeda: Center for Advanced Oral Science, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, Japan
Koichi Tabeta: Division of Periodontology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, Japan
Triantafyllos Chavakis: Institute for Clinical Chemistry and Laboratory Medicine, University Hospital and Faculty of Medicine, Technische Universität Dresden, Dresden, Germany; Centre for Cardiovascular Science, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK
George Hajishengallis: Department of Basic and Translational Sciences, Laboratory of Innate Immunity and Inflammation, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Tomoki Maekawa: Center for Advanced Oral Science, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, Japan; Corresponding author

Journal volume & issue: Vol. 27, no. 2
p. 108798

Abstract

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Summary: Aging is associated with increased susceptibility to chronic inflammatory bone loss disorders, such as periodontitis, in large part due to the impaired regenerative potential of aging tissues. DEL-1 exerts osteogenic activity and promotes bone regeneration. However, DEL-1 expression declines with age. Here we show that systemically administered macrolide antibiotics and a non-antibiotic erythromycin derivative, EM-523, restore DEL-1 expression in 18-month-old (“aged”) mice while promoting regeneration of bone lost due to naturally occurring age-related periodontitis. These compounds failed to induce bone regeneration in age-matched DEL-1-deficient mice. Consequently, these drugs promoted DEL-1-dependent functions, including alkaline phosphatase activity and osteogenic gene expression in the periodontal tissue while inhibiting osteoclastogenesis, leading to net bone growth. Macrolide-treated aged mice exhibited increased skeletal bone mass, suggesting that this treatment may be pertinent to systemic bone loss disorders. In conclusion, we identified a macrolide–DEL-1 axis that can regenerate bone lost due to aging-related disease.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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