Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Am J Sports Med. 2022 Jul;50(9):2488-2496. doi: 10.1177/03635465221098133. Epub 2022 Jun 6.
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.
To assess whether celecoxib can prevent the inflamm-aging-related cellular senescence of TDSCs.
Controlled laboratory study.
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.
S-TDSCs showed increased senescence-associated β-galactosidase activity and enhanced expression of , , , 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.
Celecoxib treatment can prevent inflamm-aging-induced TDSC senescence, which holds potential for alleviating the development of degenerative RCT.
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.
退行性肩袖肌腱病（RCT）与肌腱源性干细胞（TDSCs）的衰老有关。非甾体抗炎药已被证明可以减轻与年龄相关的炎症（炎性衰老）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性衰老相关的 TDSC 衰老来减轻退行性 RCT 仍然未知。
评估塞来昔布是否可以预防 TDSC 的炎性衰老相关细胞衰老。
对照实验室研究。
从退行性 RCT 肌腱（S-TDSCs）和健康的腘绳肌腱（Y-TDSCs）中分离 TDSC，并评估 TDSC 的细胞衰老。然后，收集衰老的 TDSC 条件培养基（SEN-CM），并用或不用塞来昔布培养 Y-TDSC。通过测定衰老相关标志物的表达来检测塞来昔布对 TDSC 衰老的影响。此外，通过 Western blot 分析测定 NF-κB 通路的水平，以探讨其潜在机制。还通过多谱系分化试验确定其对预防炎性衰老诱导的衰老 TDSC 功能障碍的影响。
S-TDSCs 显示出增加的衰老相关β-半乳糖苷酶活性和增强的表达、、、和衰老相关分泌表型因子。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，塞来昔布治疗可以预防炎性衰老对 Y-TDSCs 的不利影响。SEN-CM 组中 NF-κB 通路的水平升高，但使用塞来昔布后降低。此外，TDSCs 的衰老减少导致 TDSC 腱形成潜能得以保留。
塞来昔布治疗可以预防炎性衰老诱导的 TDSC 衰老，这可能有助于减轻退行性 RCT 的发展。
除了缓解 RCT 患者的症状外，使用塞来昔布等常见的非甾体抗炎药治疗可能通过延迟 TDSC 衰老来延缓 RCT 的发展并预防肩袖撕裂。
