Lui Pauline Po Yee, Wong Chi Ming
Headquarter, Hospital Authority, Hong Kong, Hong Kong.
Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong, Hong Kong.
Front Genet. 2020 Jan 16;10:1338. doi: 10.3389/fgene.2019.01338. eCollection 2019.
Both tendon injuries and tendinopathies, particularly rotator cuff tears, increase with tendon aging. Tendon stem cells play important roles in promoting tendon growth, maintenance, and repair. Aged tendons show a decline in regenerative potential coupled with a loss of stem cell function. Recent studies draw attention to aging primarily a disorder of stem cells. The micro-environment ("niche") where stem cells resided provides signals that direct them to metabolize, self-renew, differentiate, or remain quiescent. These signals include receptors and secreted soluble factors for cell-cell communication, extracellular matrix, oxidative stress, and vascularity. Both intrinsic cellular deficits and aged niche, coupled with age-associated systemic changes of hormonal and metabolic signals can inhibit or alter the functions of tendon stem cells, resulting in reduced fitness of these primitive cells and hence more frequent injuries and poor outcomes of tendon repair. This review aims to summarize the biological changes of aged tendons. The biological changes of tendon stem cells in aging are reviewed after a systematic search of the PubMed. Relevant factors of stem cell aging including cell-intrinsic factors, changes of microenvironment, and age-associated systemic changes of hormonal and metabolic signals are examined, with findings related to tendon stem cells highlighted when literature is available. Future research directions on the aging mechanisms of tendon stem cells are discussed. Better understanding of the molecular mechanisms underlying the functional decline of aged tendon stem cells would provide insight for the rational design of rejuvenating therapies.
肌腱损伤和肌腱病，尤其是肩袖撕裂，都随着肌腱老化而增加。肌腱干细胞在促进肌腱生长、维持和修复中发挥着重要作用。老化的肌腱再生潜力下降，同时干细胞功能丧失。最近的研究将衰老主要视为一种干细胞紊乱。干细胞所处的微环境（“生态位”）提供信号，指导它们进行代谢、自我更新、分化或保持静止。这些信号包括用于细胞间通讯的受体和分泌的可溶性因子、细胞外基质、氧化应激和血管形成。内在的细胞缺陷和老化的生态位，再加上与年龄相关的激素和代谢信号的全身变化，会抑制或改变肌腱干细胞的功能，导致这些原始细胞的适应性降低，从而使肌腱损伤更频繁，肌腱修复的效果更差。这篇综述旨在总结老化肌腱的生物学变化。在对PubMed进行系统检索后，对衰老过程中肌腱干细胞的生物学变化进行了综述。研究了干细胞衰老的相关因素，包括细胞内在因素、微环境变化以及与年龄相关的激素和代谢信号的全身变化，当有相关文献时，突出显示与肌腱干细胞相关的研究结果。讨论了肌腱干细胞衰老机制的未来研究方向。更好地理解老化肌腱干细胞功能下降的分子机制将为恢复活力疗法的合理设计提供思路。
