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

Age Immunology Small molecule

Journal

iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038

Informations de publication

Date de publication:
16 Feb 2024
Historique:
received: 15 09 2023
revised: 24 10 2023
accepted: 02 01 2024
medline: 23 1 2024
pubmed: 23 1 2024
entrez: 23 1 2024
Statut: epublish

Résumé

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.

Identifiants

DOI: 10.1016/j.isci.2024.108798 PMID: 38261928 PMC: PMC10797555
pubmed: 38261928
doi: 10.1016/j.isci.2024.108798
pii: S2589-0042(24)00019-1
pmc: PMC10797555
doi:

Types de publication

Journal Article

Langues

eng

Pagination

108798

Informations de copyright

© 2024 The Author(s).

Déclaration de conflit d'intérêts

The authors declare no conflict of interest.

Auteurs

Kridtapat Sirisereephap (K)

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 (H)

Center for Advanced Oral Science, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, Japan.

Jong-Hyung Lim (JH)

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 (MDC)

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 (T)

Division of Microbiology and Infectious Diseases, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, Japan.

Takumi Hiyoshi (T)

Center for Advanced Oral Science, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, Japan.

Andrea L Rosenkranz (AL)

Center for Advanced Oral Science, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, Japan.

Yurie Sato-Yamada (Y)

Center for Advanced Oral Science, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, Japan.

Hisanori Domon (H)

Division of Microbiology and Infectious Diseases, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, Japan.

Akari Ikeda (A)

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 (T)

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 (T)

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 (N)

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 (H)

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 (Y)

Division of Microbiology and Infectious Diseases, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, Japan.

Takeyasu Maeda (T)

Center for Advanced Oral Science, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, Japan.

Koichi Tabeta (K)

Division of Periodontology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, Japan.

Triantafyllos Chavakis (T)

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 (G)

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 (T)

Center for Advanced Oral Science, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, Japan.

Classifications MeSH