Enhanced Circadian Clock in MSCs-Based Cytotherapy Ameliorates Age-Related Temporomandibular Joint Condyle Degeneration.
Enhanced Circadian Clock in MSCs-Based Cytotherapy Ameliorates Age-Related Temporomandibular Joint Condyle Degeneration.
复制标题
基于间充质干细胞的细胞疗法中增强的昼夜节律可改善与年龄相关的颞下颌关节髁变性
DOI：
10.3390/ijms221910632
复制
发表时间：
2021-09-30
影响因子：
5.6
通讯作者：
Bai D
中科院分区：
文献类型：
--
作者：
Cha S;Lee SM;Wang J;Zhao Q;Bai D
衰老已被证明是老年人颞下颌关节（TMJ）残疾和疼痛的主要原因之一。外周昼夜节律在软骨内成骨和软骨形成中起着至关重要的作用。然而，颞下颌关节结构中与年龄相关的生物钟改变很少报道。在本研究中，我们分别从幼年（4月龄）、中年（10月龄）和老年（20月龄）的成年人中提取TMJ髁突，以检测TMJ髁突形态和昼夜振荡随年龄增长的变化。研究人员对bmal1缺失骨髓间充质干细胞（BMSCs）和对照组的转录组谱进行了研究，以揭示分子水平上与昼夜节律相关的差异。此外，体外和体内研究了bmal1过表达bmscs细胞疗法对老年TMJ髁的修复作用。衰老的TMJ髁表现为组织结构受损和昼夜节律紊乱，并伴有软骨形成能力和骨转换活动的逐渐下降。Bmal1的缺失显著下调了软骨形成相关基因Prg4、Sox9和Col7a1。bmal1过表达的骨髓间充质干细胞体外迁移能力增强，体内年龄相关性TMJ髁变性减弱。这些数据证明了昼夜节律在维持骨软骨稳态中的关键作用，并表明了昼夜节律修饰的MSCs治疗在组织再生中的潜在临床前景。
Aging has been proven to be one of the major causes of temporomandibular joint (TMJ) disability and pain in older people. Peripheral circadian rhythms play a crucial role in endochondral ossification and chondrogenesis. However, the age-related alterations of circadian clock in TMJ structures are seldom reported. In the current study, TMJ condyles were extracted from young (4-month-old), middle-aged (10-month-old), and old-aged (20-month-old) adults to detect the morphology and circadian oscillation changes in TMJ condyles with aging. The transcriptome profile of Bmal1-deleted bone-marrow mesenchymal stem cells (BMSCs) and controls were explored to reveal the circadian-related differences at the molecular level. Furthermore, the reparative effects of Bmal1-overexpressed BMSCs-based cytotherapy in aged TMJ condyles were investigated in vitro and in vivo. Aged TMJ condyles displayed damaged tissue structure and an abolished circadian rhythm, accompanied by a progressively decreasing chondrogenesis capability and bone turnover activities. The deletion of Bmal1 significantly down-regulated chondrogenesis-related genes Prg4, Sox9, and Col7a1. Bmal1-overexpressed BMSCs presented improved migration capability ex vivo and attenuated age-related TMJ condylar degeneration in vivo. These data demonstrate the crucial role of circadian timing in the maintenance of osteochondral homeostasis, and indicate the potential clinical prospects of circadian-modified MSCs therapy in tissue regeneration.
登录
查看更多内容
昼夜节律对衰老和寿命的重要性。
影响因子：
16.6
作者：
Acosta-Rodríguez VA;Rijo-Ferreira F;Green CB;Takahashi JS
通讯作者：
Takahashi JS
影响因子：
8.5
作者：
He, Y.;Chen, Y.;Tan, Z.
通讯作者：
Tan, Z.
IGF-1 通过分泌卷曲相关蛋白 2 途径增强心肌梗死中 BMSC 的活力、迁移和抗凋亡作用
影响因子：
7.5
作者：
Lin, Mingzhuo;Liu, Xinyue;Huang, Yuli
通讯作者：
Huang, Yuli
DOI：
10.1016/j.tripleo.2009.02.023
发表时间：
2009-06-01
期刊：
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTOLOGY
影响因子：
--
作者：
Ahmad, Mansur;Hollender, Lars;Schiffman, Eric L.
通讯作者：
Schiffman, Eric L.
影响因子：
4.1
作者：
Lotz M;Loeser RF
通讯作者：
Loeser RF