塞来昔布缓解退行性肩袖肌腱病变中肌腱源性干细胞衰老的作用研究

Abstract

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, p21CIP1A, p16INK4A, 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 Rel