Chen Xin, Ji Xing, Lao Zhaobai, Pan Bin, Qian Yu, Yang Wanlei
Department of Orthopedics Surgery, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, 310006, China.
Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, Department of Clinical Medicine, School of Medicine, Hangzhou City University, Hangzhou, Zhejiang, China.
J Orthop Translat. 2025 Jan 20;51:13-23. doi: 10.1016/j.jot.2024.12.003. eCollection 2025 Mar.
Wolff's Law and the Mechanostat Theory elucidate how bone tissues detect and convert mechanical stimuli into biological signals, crucial for maintaining bone equilibrium. Abnormal mechanics can lead to diseases such as osteoporosis, osteoarthritis, and nonunion fractures. However, the detailed molecular mechanisms by which mechanical cues are transformed into biological responses in bone remain underexplored. Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), key regulators of bone homeostasis, are instrumental in this process. Emerging research highlights bone cells' ability to sense various mechanical stimuli and relay these signals intracellularly. YAP/TAZ are central in receiving these mechanical cues and converting them into signals that influence bone cell behavior. Abnormal YAP/TAZ activity is linked to several bone pathologies, positioning these proteins as promising targets for new treatments. Thus, this review aims to provide an in-depth examination of YAP/TAZ's critical role in the interpretation of mechanical stimuli to biological signals, with a special emphasis on their involvement in bone cell mechanosensing, mechanotransduction, and mechanoresponse. The translational potential of this article: Clinically, appropriate stress stimulation promotes fracture healing, while bed rest can lead to disuse osteoporosis and excessive stress can cause osteoarthritis or bone spurs. Recent advancements in the understanding of YAP/TAZ-mediated mechanobiological signal transduction in bone diseases have been significant, yet many aspects remain unknown. This systematic review summarizes current research progress, identifies unaddressed areas, and highlights potential future research directions. Advancements in this field facilitate a deeper understanding of the molecular mechanisms underlying bone mechanics regulation and underscore the potential of YAP/TAZ as therapeutic targets for bone diseases such as fractures, osteoporosis, and osteoarthritis.
沃尔夫定律和机械ostat理论阐明了骨组织如何检测机械刺激并将其转化为生物信号，这对于维持骨平衡至关重要。异常力学可导致骨质疏松症、骨关节炎和骨折不愈合等疾病。然而，机械信号在骨中转化为生物反应的详细分子机制仍未得到充分探索。Yes相关蛋白（YAP）和含PDZ结合基序的转录共激活因子（TAZ）是骨稳态的关键调节因子，在这一过程中发挥着重要作用。新兴研究突出了骨细胞感知各种机械刺激并在细胞内传递这些信号的能力。YAP/TAZ在接收这些机械信号并将其转化为影响骨细胞行为的信号方面起着核心作用。YAP/TAZ活性异常与多种骨病理相关，使这些蛋白质成为新治疗方法的有希望的靶点。因此，本综述旨在深入探讨YAP/TAZ在将机械刺激转化为生物信号中的关键作用，特别强调它们在骨细胞机械传感、机械转导和机械反应中的参与。本文的转化潜力：临床上，适当的应力刺激促进骨折愈合，而卧床休息可导致废用性骨质疏松症，过度应力可导致骨关节炎或骨赘。在理解YAP/TAZ介导的骨疾病机械生物学信号转导方面，最近取得了重大进展，但许多方面仍不清楚。本系统综述总结了当前的研究进展，确定了未解决的领域，并突出了潜在的未来研究方向。该领域的进展有助于更深入地理解骨力学调节的分子机制，并强调YAP/TAZ作为骨折、骨质疏松症和骨关节炎等骨疾病治疗靶点的潜力。
