Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center, College of Basic Medicine, Chongqing Medical University, Chongqing 400016, China.
Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 401331, China.
Cells. 2022 Dec 16;11(24):4091. doi: 10.3390/cells11244091.
Diabetes-associated bone complications lead to fragile bone mechanical strength and osteoporosis, aggravating the disease burden of patients. Advanced evidence shows that chronic hyperglycemia and metabolic intermediates, such as inflammatory factor, reactive oxygen species (ROS), and advanced glycation end products (AGEs), are regarded as dominant hazardous factors of bone complications, whereas the pathophysiological mechanisms are complex and controversial. By establishing a diabetic Sprague-Dawley (SD) rat model and diabetic bone loss cell model in vitro, we confirmed that diabetes impaired primary cilia and led to bone loss, while adding Icariin (ICA) could relieve the inhibitions. Mechanistically, ICA could scavenge ROS to maintain the mitochondrial and primary cilia homeostasis of osteoblasts. Intact primary cilia acted as anchoring and modifying sites of Gli2, thereby activating the primary cilia/Gli2/osteocalcin signaling pathway to promote osteoblast differentiation. All results suggest that ICA has potential as a therapeutic drug targeting bone loss induced by diabetes.
糖尿病相关的骨骼并发症导致骨骼机械强度变脆弱和骨质疏松，加重了患者的疾病负担。现有证据表明，慢性高血糖和代谢中间产物（如炎症因子、活性氧（ROS）和晚期糖基化终产物（AGEs））被认为是骨骼并发症的主要危险因子，然而其病理生理机制复杂且存在争议。通过建立糖尿病 Sprague-Dawley（SD）大鼠模型和体外糖尿病性骨丢失细胞模型，我们证实糖尿病会损害初级纤毛，导致骨丢失，而添加淫羊藿苷（ICA）则可以缓解这种抑制作用。从机制上讲，ICA 可以清除 ROS 以维持成骨细胞的线粒体和初级纤毛稳态。完整的初级纤毛充当 Gli2 的锚定点和修饰点，从而激活初级纤毛/Gli2/骨钙素信号通路，促进成骨细胞分化。所有结果均表明，ICA 可能成为一种针对糖尿病引起的骨丢失的治疗药物。
