Chen Shih-Yao, Jou I-Ming, Ko Po-Yen, Hsu Kai-Lan, Su Wei-Ren, Kuo Li-Chieh, Lee Pei-Yuan, Wu Chao-Liang, Wu Po-Ting
Department of Nursing, College of Nursing, Chung Hwa University of Medical Technology, Tainan 71703, Taiwan.
Department of Orthopaedics, E-Da Hospital, Kaohsiung 82445, Taiwan.
Mol Ther Methods Clin Dev. 2022 Jun 10;26:157-168. doi: 10.1016/j.omtm.2022.06.006. eCollection 2022 Sep 8.
CD44 exerts anti-senescence effects in many disease models. We examined senescence in tendinopathy and the effect of CD44 on senescence-associated secretory phenotypes (SASPs). Senescent markers were determined in human tendinopathic long head of bicep (LHB) and normal hamstring tendons. CD44 gene transfer in rat tendinopathic tenocytes stimulated with interleukin (IL)-1β and a rat Achilles tendinopathy model were performed using lentiviral vectors. Expression levels of p53, p21, and p16 and senescence-associated β-galactosidase (SA-β-gal) activity were positively correlated with the severity of human tendinopathy and were higher in rat and human tendinopathic tenocytes than in normal controls. CD44 overexpressed tenocyte transfectants exhibited reduced levels of IL-6, matrix metalloproteinases (MMPs), cyclooxygenase (COX)-2, p53, p21, p16, SA-β-gal, and phospho-nuclear factor (NF)-κB, whereas their collagen type I alpha 1 (COL1A1) and tenomodulin (tnmd) levels were increased when compared with control transfectants under IL-1β-stimulated conditions. In the animal model, CD44 overexpression lowered the ultrasound and histology scores and expression levels of the senescent and SASP markers COX-2 and phospho-NF-κB. Bromodeoxyuridine (BrdU)- and tnmd-positive cell numbers were increased in the LVCD44-transduced tendinopathic tendons. Senescence is positively correlated with tendinopathic severity, and CD44 overexpression may protect the tendinopathic tendons from SASPs via anti-inflammation and maintenance of extracellular matrix homeostasis.
CD44在许多疾病模型中发挥抗衰老作用。我们研究了肌腱病中的衰老情况以及CD44对衰老相关分泌表型（SASP）的影响。在人类肱二头肌长头肌腱病（LHB）和正常绳肌腱中测定衰老标志物。使用慢病毒载体在白细胞介素（IL）-1β刺激的大鼠肌腱病性肌腱细胞中进行CD44基因转移，并建立大鼠跟腱肌腱病模型。p53、p21和p16的表达水平以及衰老相关β-半乳糖苷酶（SA-β-gal）活性与人类肌腱病的严重程度呈正相关，在大鼠和人类肌腱病性肌腱细胞中高于正常对照组。与对照转染细胞相比，在IL-1β刺激条件下，过表达CD44的肌腱细胞转染子中IL-6、基质金属蛋白酶（MMP）、环氧化酶（COX）-2、p53、p21、p16、SA-β-gal和磷酸化核因子（NF）-κB水平降低，而其I型胶原α1（COL1A1）和肌腱调节蛋白（tnmd）水平升高。在动物模型中，CD44过表达降低了超声和组织学评分以及衰老和SASP标志物COX-2和磷酸化NF-κB的表达水平。在LVCD44转导的肌腱病性肌腱中，溴脱氧尿苷（BrdU）和tnmd阳性细胞数量增加。衰老与肌腱病严重程度呈正相关，CD44过表达可能通过抗炎和维持细胞外基质稳态来保护肌腱病性肌腱免受SASP影响。
