Icariin Treatment Rescues Diabetes Induced Bone Loss via Scavenging ROS and Activating Primary Cilia/Gli2/Osteocalcin Signaling Pathway
Jie Liu,
Qingfeng Cheng,
Xiangmei Wu,
Huifang Zhu,
Xiaoyan Deng,
Maorong Wang,
Shengyong Yang,
Jie Xu,
Qian Chen,
Mengxue Li,
Xianjun Liu,
Changdong Wang
Affiliations
Jie Liu
Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center, College of Basic Medicine, Chongqing Medical University, Chongqing 400016, China
Qingfeng Cheng
Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 401331, China
Xiangmei Wu
Department of Physiology, Molecular Medicine and Cancer Research Center, College of Basic Medicine, Chongqing Medical University, Chongqing 400016, China
Huifang Zhu
Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center, College of Basic Medicine, Chongqing Medical University, Chongqing 400016, China
Xiaoyan Deng
Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center, College of Basic Medicine, Chongqing Medical University, Chongqing 400016, China
Maorong Wang
Department of Endocrinology, Affiliated Hospital of Hubei University for Nationalities, Enshi 445000, China
Shengyong Yang
Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center, College of Basic Medicine, Chongqing Medical University, Chongqing 400016, China
Jie Xu
Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center, College of Basic Medicine, Chongqing Medical University, Chongqing 400016, China
Qian Chen
Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center, College of Basic Medicine, Chongqing Medical University, Chongqing 400016, China
Mengxue Li
Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center, College of Basic Medicine, Chongqing Medical University, Chongqing 400016, China
Xianjun Liu
Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center, College of Basic Medicine, Chongqing Medical University, Chongqing 400016, China
Changdong Wang
Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center, College of Basic Medicine, Chongqing Medical University, Chongqing 400016, China
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.
