Benage Lindsay G, Sweeney James D, Giers Morgan B, Balasubramanian Ravi
School of Chemical, Biological and Environmental Engineering, Oregon State University, Corvallis, OR, United States.
School of Mechanical, Industrial and Manufacturing Engineering, Oregon State University, Corvallis, OR, United States.
Front Bioeng Biotechnol. 2022 Jul 15;10:896336. doi: 10.3389/fbioe.2022.896336. eCollection 2022.
Dynamic loading is a shared feature of tendon tissue homeostasis and pathology. Tendon cells have the inherent ability to sense mechanical loads that initiate molecular-level mechanotransduction pathways. While mature tendons require physiological mechanical loading in order to maintain and fine tune their extracellular matrix architecture, pathological loading initiates an inflammatory-mediated tissue repair pathway that may ultimately result in extracellular matrix dysregulation and tendon degeneration. The exact loading and inflammatory mechanisms involved in tendon healing and pathology is unclear although a precise understanding is imperative to improving therapeutic outcomes of tendon pathologies. Thus, various model systems have been designed to help elucidate the underlying mechanisms of tendon mechanobiology mimicry of the tendon architecture and biomechanics. Recent development of model systems has focused on identifying mechanoresponses to various mechanical loading platforms. Less effort has been placed on identifying inflammatory pathways involved in tendon pathology etiology, though inflammation has been implicated in the onset of such chronic injuries. The focus of this work is to highlight the latest discoveries in tendon mechanobiology platforms and specifically identify the gaps for future work. An interdisciplinary approach is necessary to reveal the complex molecular interplay that leads to tendon pathologies and will ultimately identify potential regenerative therapeutic targets.
动态加载是肌腱组织稳态和病理过程的一个共同特征。肌腱细胞具有感知机械负荷的内在能力,这些负荷会启动分子水平的机械转导途径。虽然成熟的肌腱需要生理机械负荷来维持和微调其细胞外基质结构,但病理性负荷会启动炎症介导的组织修复途径,最终可能导致细胞外基质失调和肌腱退变。尽管准确理解对于改善肌腱疾病的治疗效果至关重要,但肌腱愈合和病理过程中涉及的确切加载和炎症机制尚不清楚。因此,人们设计了各种模型系统来帮助阐明肌腱机械生物学的潜在机制,模拟肌腱结构和生物力学。模型系统的最新发展集中在确定对各种机械加载平台的机械反应。虽然炎症与这类慢性损伤的发病有关,但在确定肌腱病理病因中涉及的炎症途径方面所做的工作较少。这项工作的重点是突出肌腱机械生物学平台的最新发现,并具体确定未来工作的空白。需要采用跨学科方法来揭示导致肌腱疾病的复杂分子相互作用,并最终确定潜在的再生治疗靶点。