Bone and joint-related diseases, including osteoarthritis (OA), rheumatoid arthritis (RA), and bone tumors, pose significant health challenges due to their debilitating effects on the musculoskeletal system. 14-3-3 proteins, a family of conserved regulatory molecules, play a critical role in the pathology of these diseases. This review discusses the intricate structure and multifunctionality of 14-3-3 proteins, their regulation of signaling pathways, and their interactions with other proteins. We underscore the significance of 14-3-3 proteins in the regulation of osteoblasts, osteoclasts, chondrocytes, and bone remodeling, all key factors in the maintenance and dysfunction of bone and joint systems. Specific focus is directed toward elucidating the contribution of 14-3-3 proteins in the pathology of OA, RA, and bone malignancies, where dysregulated 14-3-3-mediated signaling cascades have been implicated in the disease processes. This review illuminates how the perturbation of 14-3-3 protein interactions can lead to the pathological manifestations observed in these disorders, including joint destruction and osteolytic activity. We highlight cutting-edge research that positions 14-3-3 proteins as potential biomarkers for disease progression and as innovative therapeutic targets, offering new avenues for disease intervention and management.

骨骼和关节相关疾病，包括骨关节炎 （OA）、类风湿性关节炎 （RA） 和骨肿瘤，由于它们对肌肉骨骼系统的衰弱影响，构成了重大的健康挑战。14-3-3 蛋白是一个保守的调节分子家族，在这些疾病的病理学中起着关键作用。本文讨论了 14-3-3 蛋白的复杂结构和多功能性、它们对信号通路的调节以及它们与其他蛋白的相互作用。我们强调了 14-3-3 蛋白在成骨细胞、破骨细胞、软骨细胞和骨重塑调节中的重要性，这些都是骨骼和关节系统维持和功能障碍的关键因素。特别关注阐明 14-3-3 蛋白在 OA、RA 和骨恶性肿瘤病理学中的贡献，其中失调的 14-3-3 介导的信号级联反应与疾病过程有关。本综述阐明了 14-3-3 蛋白相互作用的扰动如何导致在这些疾病中观察到的病理表现，包括关节破坏和溶骨活性。我们重点介绍了将 14-3-3 蛋白定位为疾病进展的潜在生物标志物和创新的治疗靶点的前沿研究，为疾病干预和管理提供了新的途径。