DEL‐1 is an Endogenous Senolytic Protein that Inhibits Senescence‐Associated Bone Loss
Source abstract
Abstract
Abstract Accumulation of senescent cells in the bone microenvironment, including bone marrow mesenchymal stromal cells (BM‐MSCs), contributes to aging‐related bone degeneration. Developmental endothelial locus‐1 (DEL‐1), the expression of which declines with old age is herein described as an endogenous secreted senolytic protein. DEL‐1 promotes apoptosis of senescent BM‐MSCs via a β3 integrin/CD73/adenosine/p38 mitogen‐activated protein kinase (p38 MAPK)/B‐cell lymphoma‐2 (BCL‐2) pathway, thereby leading to their clearance by macrophages. DEL‐1‐deficiency displays increased abundance of β3 integrin‐rich CD73 + senescent BM‐MSCs and higher chemotherapy‐induced or aging‐related senescence‐associated bone loss. Conversely, mice with endothelial‐specific overexpression of DEL‐1 (EC‐Del1) have decreased numbers of senescent BM‐MSCs and diminish senescence‐associated bone loss. CD73‐deficiency reverses the reduction in senescent BM‐MSC numbers in EC‐Del1 mice. Administration of DEL‐1 (or a DEL‐1‐inducing macrolide) causes a reduction in senescence markers and reverses aging‐related periodontitis. Therefore, DEL‐1 may be harnessed as an endogenous senolytic to prevent senescent cell buildup and senescence‐associated bone loss.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Adenosine and Purinergic Signaling · Telomeres, Telomerase, and Senescence · Neutrophil, Myeloperoxidase and Oxidative Mechanisms
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Department of Basic and Translational Sciences Laboratory of Innate Immunity and Inflammation Penn Dental Medicine University of Pennsylvania Philadelphia PA 19104 USA
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
West China Hospital of Stomatology Sichuan University Chengdu 610041 Sichuan China
Institute for Clinical Chemistry and Laboratory Medicine University Hospital and Faculty of Medicine Technische Universität Dresden 01307 Dresden Germany
National Center for Tumor Diseases Partner Site Dresden 01307 Dresden Germany
Department of Periodontics Penn Dental Medicine University of Pennsylvania Philadelphia PA 19104 USA
Department of Periodontology and Endodontology Tohoku University Graduate School of Dentistry Sendai 980‐8575 Japan
Sheng Yushou Center of Cell Biology and Immunology School of Life Sciences and Biotechnology Shanghai Jiao Tong University Shanghai 200240 China
Funding
Japan Agency for Medical Research and Development · Mochida Memorial Foundation for Medical and Pharmaceutical Research · Japan Society for the Promotion of Science · National Institute of Dental and Craniofacial Research
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