{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1360021391870851968.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1016/j.isci.2024.108798"}},{"identifier":{"@type":"URI","@value":"https://api.elsevier.com/content/article/PII:S2589004224000191?httpAccept=text/xml"}},{"identifier":{"@type":"URI","@value":"https://api.elsevier.com/content/article/PII:S2589004224000191?httpAccept=text/plain"}},{"identifier":{"@type":"DOI","@value":"10.60692/wz3sn-ed862"}},{"identifier":{"@type":"DOI","@value":"10.60692/jr2zg-tm747"}}],"resourceType":"学術雑誌論文(journal article)","dc:title":[{"@value":"A novel macrolide–Del-1 axis to regenerate bone in old age"}],"description":[{"notation":[{"@value":"El envejecimiento se asocia con una mayor susceptibilidad a los trastornos inflamatorios crónicos de pérdida ósea, como la periodontitis, en gran parte debido al potencial regenerativo deteriorado de los tejidos envejecidos. DEL-1 ejerce actividad osteogénica y promueve la regeneración ósea. Sin embargo, la expresión de DEL-1 disminuye con la edad. Aquí mostramos que los antibióticos macrólidos administrados sistémicamente y un derivado de eritromicina no antibiótico, EM-523, restauran la expresión de DEL-1 en ratones de 18 meses de edad (\"envejecidos\") al tiempo que promueven la regeneración de la pérdida ósea debido a la periodontitis relacionada con la edad de origen natural. Estos compuestos no lograron inducir la regeneración ósea en ratones deficientes en DEL-1 de la misma edad. En consecuencia, estos fármacos promovieron las funciones dependientes de DEL-1, incluida la actividad de la fosfatasa alcalina y la expresión génica osteogénica en el tejido periodontal, al tiempo que inhibieron la osteoclastogénesis, lo que condujo al crecimiento óseo neto. Los ratones envejecidos tratados con macrólidos mostraron un aumento de la masa ósea esquelética, lo que sugiere que este tratamiento puede ser pertinente para los trastornos de pérdida ósea sistémica. En conclusión, identificamos un eje macrólido-DEL-1 que puede regenerar la pérdida ósea debido a enfermedades relacionadas con el envejecimiento."}]},{"notation":[{"@value":"Le vieillissement est associé à une sensibilité accrue aux troubles inflammatoires chroniques de la perte osseuse, tels que la parodontite, en grande partie en raison du potentiel régénérateur altéré des tissus vieillissants. DEL-1 exerce une activité ostéogénique et favorise la régénération osseuse. Cependant, l'expression de DEL-1 diminue avec l'âge. Ici, nous montrons que les antibiotiques macrolides administrés par voie systémique et un dérivé non antibiotique de l'érythromycine, EM-523, rétablissent l'expression de DEL-1 chez les souris de 18 mois (« âgées ») tout en favorisant la régénération des os perdus en raison d'une parodontite naturelle liée à l'âge. Ces composés n'ont pas réussi à induire la régénération osseuse chez des souris déficientes en DEL-1 d'âge correspondant. Par conséquent, ces médicaments ont favorisé les fonctions DEL-1-dépendantes, y compris l'activité de la phosphatase alcaline et l'expression des gènes ostéogéniques dans le tissu parodontal tout en inhibant l'ostéoclastogenèse, conduisant à une croissance osseuse nette. Les souris âgées traitées aux macrolides présentaient une augmentation de la masse osseuse squelettique, ce qui suggère que ce traitement peut être pertinent pour les troubles systémiques de la perte osseuse. En conclusion, nous avons identifié un axe macrolide-DEL-1 qui peut régénérer les os perdus en raison de maladies liées au vieillissement."}]},{"notation":[{"@value":"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."}]},{"notation":[{"@value":"ترتبط الشيخوخة بزيادة القابلية للإصابة باضطرابات فقدان العظام الالتهابية المزمنة، مثل التهاب اللثة، ويرجع ذلك إلى حد كبير إلى ضعف القدرة التجددية لأنسجة الشيخوخة. يمارس DEL -1 نشاطًا عظمي المنشأ ويعزز تجديد العظام. ومع ذلك، فإن تعبير DEL -1 ينخفض مع تقدم العمر. نوضح هنا أن المضادات الحيوية الماكروليدية التي يتم إعطاؤها بشكل منهجي ومشتق الإريثروميسين غير المضاد للمضادات الحيوية، EM -523، تستعيد تعبير DEL -1 في الفئران البالغة من العمر 18 شهرًا (\" العمر \") مع تعزيز تجديد العظام المفقودة بسبب التهاب اللثة المرتبط بالعمر بشكل طبيعي. فشلت هذه المركبات في تحفيز تجديد العظام في الفئران التي تعاني من نقص DEL -1 المطابقة للعمر. وبالتالي، عززت هذه الأدوية الوظائف المعتمدة على DEL -1، بما في ذلك نشاط الفوسفاتيز القلوي والتعبير الجيني العظمي في أنسجة اللثة مع تثبيط تكوين الخلايا البدائية العظمية، مما يؤدي إلى نمو العظام الصافي. أظهرت الفئران المسنة المعالجة بماكروليد زيادة في كتلة عظام الهيكل العظمي، مما يشير إلى أن هذا العلاج قد يكون ذا صلة باضطرابات فقدان العظام الجهازية. في الختام، حددنا محور ماكروليد- ديل-1 الذي يمكن أن يجدد العظام المفقودة بسبب الأمراض المرتبطة بالشيخوخة."}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380021391870852125","@type":"Researcher","foaf:name":[{"@value":"Kridtapat Sirisereephap"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021391870852139","@type":"Researcher","foaf:name":[{"@value":"Hikaru Tamura"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021391870851998","@type":"Researcher","foaf:name":[{"@value":"Jong-Hyung Lim"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021391870851977","@type":"Researcher","foaf:name":[{"@value":"Meircurius Dwi Condro Surboyo"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021391870851972","@type":"Researcher","foaf:name":[{"@value":"Toshihito Isono"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021391870851993","@type":"Researcher","foaf:name":[{"@value":"Takumi Hiyoshi"}]},{"@id":"https://cir.nii.ac.jp/crid/1380021391870852011","@type":"Researcher","foaf:name":[{"@value":"Andrea L. 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