Background:

Degenerative rotator cuff tendinopathy (RCT) is associated with the senescence of tendon-derived stem cells (TDSCs). Nonsteroidal anti-inflammatory drugs have been demonstrated to alleviate age-associated inflammation (inflamm-aging)–induced cellular senescence of skeletal stem/progenitor cells. However, whether they can alleviate degenerative RCT through reducing inflamm-aging–related TDSC senescence is still unknown.

Purpose:

To assess whether celecoxib can prevent the inflamm-aging–related cellular senescence of TDSCs.

Study Design:

Controlled laboratory study.

Methods:

TDSCs were isolated from degenerative RCT tendons (S-TDSCs) and healthy hamstring tendons (Y-TDSCs), and the cellular senescence of TDSCs was evaluated. Thereafter, the senescent TDSC-conditioned medium (SEN-CM) was collected to culture Y-TDSCs with or without celecoxib. The effects of celecoxib on TDSC senescence were examined by assaying the expression of aging-related markers. Furthermore, the level of the NF-κB pathway was determined by Western blot analysis to explore the underlying mechanism. Its effects on preventing dysfunction of inflamm-aging–induced senescent TDSCs were also determined using multilineage differentiation assay.

Results:

S-TDSCs showed increased senescence-associated β-galactosidase activity and enhanced expression of γ-H2AX, p21^CIP1A, p16^INK4A, and senescence-associated secretory phenotype factors. SEN-CM accelerated the senescence progress of Y-TDSCs, resulting in an increase in senescence markers. To some extent, celecoxib treatment could prevent the detrimental effects of inflamm-aging on Y-TDSCs. The level of the NF-κB pathway was increased in the SEN-CM group but decreased with the use of celecoxib. Moreover, the reduced senescence of TDSCs resulted in preservation of the TDSC tenogenic potential.

Conclusion:

Celecoxib treatment can prevent inflamm-aging–induced TDSC senescence, which holds potential for alleviating the development of degenerative RCT.

Clinical Relevance:

In addition to relieving the symptoms of patients with RCT, treatment with celecoxib, a common nonsteroidal anti-inflammatory drug, may defer the development of RCT and prevent rotator cuff tears by delaying TDSC senescence.

中文翻译：

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塞来昔布，超越抗炎，减轻退行性肩袖肌腱病中肌腱源性干细胞衰老

背景：

退行性肩袖肌腱病 (RCT) 与肌腱干细胞 (TDSC) 的衰老有关。非甾体类抗炎药已被证明可以减轻与年龄相关的炎症（炎症老化）诱导的骨骼干/祖细胞的细胞衰老。然而，它们是否可以通过减少与炎症老化相关的 TDSC 衰老来缓解退行性 RCT 仍是未知数。

目的：

评估塞来昔布是否可以预防 TDSC 的炎症老化相关细胞衰老。

学习规划：

受控实验室研究。

方法：

从退行性 RCT 肌腱 (S-TDSCs) 和健康腘绳肌腱 (Y-TDSCs) 中分离出 TDSCs，并评估 TDSCs 的细胞衰老。此后，收集衰老的 TDSC 条件培养基 (SEN-CM) 以培养含有或不含塞来昔布的 Y-TDSC。通过测定衰老相关标志物的表达来检查塞来昔布对TDSC衰老的影响。此外，通过蛋白质印迹分析确定NF-κB途径的水平以探索潜在机制。还使用多向分化测定法确定了其对预防炎症老化诱导的衰老 TDSC 功能障碍的影响。

结果：

S-TDSCs 显示出与衰老相关的 β-半乳糖苷酶活性增加和γ-H2AX、p21 ^CIP1A、p16 ^INK4A和衰老相关分泌表型因子的表达增强。SEN-CM 加速了 Y-TDSCs 的衰老进程，导致衰老标志物增加。在某种程度上，塞来昔布治疗可以防止炎症老化对 Y-TDSCs 的不利影响。SEN-CM 组的 NF-κB 通路水平升高，但随着塞来昔布的使用而降低。此外，TDSCs 的衰老减少导致 TDSC 致腱潜能得以保留。

结论：

塞来昔布治疗可以预防炎症老化诱导的 TDSC 衰老，这具有缓解退行性 RCT 发展的潜力。

临床相关性：

除了缓解 RCT 患者的症状外，使用塞来昔布（一种常见的非甾体抗炎药）治疗可能会延缓 RCT 的发展，并通过延缓 TDSC 衰老来预防肩袖撕裂。