PDF(Pubmed)
Abstract：
Aging is an independent risk factor for recurrent tearing after surgical repair of rotator cuff ruptures around the tendon-to-bone area. However, aging signature factors and related mechanisms involved in the healing of the rotator cuff are still unknown. We hypothesized that differences in proteins involved in the rotator cuff according to age may affect tendon-to-bone healing. The proteome analysis performed to identify the signature aging proteins of the rotator cuff confirmed the sirtuin signal as an age-specific protein. In particular, the expression of SIRT6 was markedly down-regulated with age. Ingenuity pathway analysis of omics data from age-dependent rat rotator cuffs and linear regression from human rotator cuffs showed SIRT6 to be closely related to the Wnt/β-catenin signal. We confirmed that overexpression of SIRT6 in the rotator cuff and primary tenocyte regulated canonical Wnt signaling by inhibiting the transcriptional expression of sclerostin, a Wnt antagonist. Finally, SIRT6 overexpression promoted tendon-to-bone healing after tenotomy with reconstruction in elderly rats. This approach is considered an effective treatment method for recovery from recurrent rotator cuff tears, which frequently occur in the elderly.
摘要：
衰老是肌腱-骨区域周围肩袖破裂手术修复后复发性撕裂的独立危险因素。然而,与肩袖愈合有关的衰老特征因素和相关机制尚不清楚。我们假设肩袖中涉及的蛋白质根据年龄的差异可能会影响腱-骨愈合。为了鉴定肩袖的特征老化蛋白而进行的蛋白质组分析证实sirtuin信号为年龄特异性蛋白。特别是,SIRT6的表达随着年龄的增长而显著下调。来自年龄依赖性大鼠旋转袖带的组学数据的独创性通路分析和来自人类旋转袖带的线性回归显示SIRT6与Wnt/β-catenin信号密切相关。我们证实SIRT6在肩袖和原代肌腱细胞中的过表达通过抑制硬化蛋白的转录表达来调节经典的Wnt信号。Wnt拮抗剂。最后,SIRT6过表达促进老年大鼠肌腱切开重建后腱骨愈合。这种方法被认为是从复发性肩袖撕裂恢复的有效治疗方法，这经常发生在老年人身上。
