The Hippo signaling pathway is a critical regulatory mechanism that plays a vital role in controlling organ size and facilitating tissue regeneration. This evolutionarily conserved pathway governs essential biological processes such as cell proliferation, differentiation, and apoptosis. At the heart of the Hippo pathway lies the Yes-associated protein 1 (YAP) and the WW domain-containing transcription regulator 1 (TAZ), both of which function as pivotal transcription factors. Their activity is negatively regulated by the Hippo pathway, thereby influencing various physiological functions.
YAP and TAZ are instrumental in several biological processes, particularly the differentiation of osteoblasts (OB) and osteoclasts (OC), cartilage homeostasis, skeletal muscle development, and regeneration. The balance of YAP/TAZ expression is crucial for maintaining healthy musculoskeletal tissues. However, when the Hippo pathway becomes dysregulated, it can lead to a host of musculoskeletal disorders. These include bone tumors, osteoporosis (OP), osteoarthritis (OA), intervertebral disc degeneration (IDD), muscular dystrophy, and rhabdomyosarcoma (RMS).
Given the significant implications of the Hippo pathway in musculoskeletal health, targeting this pathway has emerged as a promising therapeutic strategy. Understanding how the Hippo pathway maintains homeostasis in bone, cartilage, and skeletal muscle is essential for developing effective treatments for related disorders. The recent review explores these mechanisms in depth, elucidating the roles of the core components of the Hippo pathway in the context of various musculoskeletal diseases.
The authors of this insightful review—Juanjuan Han, Jiale Zhang, Xiaoyi Zhang, Wenxin Luo, Lifei Liu, Yuqing Zhu, Qingfeng Liu, and Xin-An Zhang—delve into the intricate interplay between YAP/TAZ activities and musculoskeletal health. They provide a comprehensive summary of how dysregulation of the Hippo pathway contributes to disease states, alongside discussing the efficacy and feasibility of Hippo pathway-related drugs as targeted therapies for musculoskeletal disorders.
With this research, the authors offer novel insights into the application of Hippo signaling in treating musculoskeletal conditions. Their findings highlight effective therapeutic targets and potential drug candidates, paving the way for future advancements in treating these prevalent health issues. Understanding the Hippo pathway’s role in maintaining tissue homeostasis not only enhances our knowledge of musculoskeletal biology but also opens new avenues for clinical intervention.
