A novel macrolide-Del-1 axis to regenerate bone in old age.
A novel macrolide-Del-1 axis to regenerate bone in old age.
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DOI：
10.1016/j.isci.2024.108798
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发表时间：
2024-02-16
期刊：
影响因子：
5.8
通讯作者：
Maekawa, Tomoki
中科院分区：
文献类型：
--
作者：
Sirisereephap, Kridtapat;Tamura, Hikaru;Lim, Jong-Hyung;Surboyo, Meircurius Dwi Condro;Isono, Toshihito;Hiyoshi, Takumi;Rosenkranz, Andrea L.;Sato-Yamada, Yurie;Domon, Hisanori;Ikeda, Akari;Hirose, Tomoyasu;Sunazuka, Toshiaki;Yoshiba, Nagako;Okada, Hiroyuki;Terao, Yutaka;Maeda, Takeyasu;Tabeta, Koichi;Chavakis, Triantafyllos;Hajishengallis, George;Maekawa, Tomoki
衰老与慢性炎症性骨质流失疾病（例如牙周炎）的易感性增加有关，这在很大程度上是由于衰老组织的再生潜力受损。 DEL-1发挥成骨活性并促进骨再生。然而，DEL-1 表达随着年龄的增长而下降。在这里，我们表明，全身给予大环内酯类抗生素和非抗生素红霉素衍生物 EM-523，可以恢复 18 个月大（“老年”）小鼠的 DEL-1 表达，同时促进因自然发生的年龄相关牙周炎而丢失的骨质再生。这些化合物未能诱导年龄匹配的 DEL-1 缺陷小鼠的骨再生。因此，这些药物促进 DEL-1 依赖性功能，包括牙周组织中的碱性磷酸酶活性和成骨基因表达，同时抑制破骨细胞生成，导致净骨生长。大环内酯治疗的老年小鼠表现出骨骼骨量增加，表明这种治疗可能与全身性骨质流失性疾病有关。总之，我们确定了一个大环内酯-DEL-1 轴，可以再生因衰老相关疾病而丢失的骨质。大环内酯类和 EM-523 增加老年小鼠牙龈和牙周组织中的 DEL-1 大环内酯类和 EM-523 促进老年骨再生 大环内酯类和 EM-523 抑制体内和体外破骨细胞生成 大环内酯类和 EM-523 诱导体内和体外成骨年龄;小分子
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. Macrolides and EM-523 increase DEL-1 in the gingiva and periodontium of aged mice Macrolides and EM-523 promote bone regeneration in old age Macrolides and EM-523 suppress osteoclastogenesis in vivo and in vitro Macrolides and EM-523 induces osteogenesis in vivo and in vitro Immunology; Age; Small molecule
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影响因子：
30.5
作者：
通讯作者：
--
影响因子：
5.6
作者：
Bassir SH;Wisitrasameewong W;Raanan J;Ghaffarigarakani S;Chung J;Freire M;Andrada LC;Intini G
通讯作者：
Intini G
影响因子：
18.6
作者：
Huang L;Salmon B;Yin X;Helms JA
通讯作者：
Helms JA
影响因子：
6
作者：
Choi, Eun Young
通讯作者：
Choi, Eun Young
影响因子：
2.2
作者：
Abe, Toshiharu;Hajishengallis, George
通讯作者：
Hajishengallis, George