Icariin Treatment Rescues Diabetes Induced Bone Loss via Scavenging ROS and Activating Primary Cilia/Gli2/Osteocalcin Signaling Pathway

Abstract

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.

Temporal control in shell–core structured nanofilm for tracheal cartilage regeneration: synergistic optimization of anti-inflammation and chondrogenesis

“…ICA, a natural compound primarily found in the Chinese herb Epimedium, demonstrates notable anti-inflammatory properties [ 44 ]. Firstly, it effectively inhibits oxidative stress reactions, mitigating the generation and harm caused by free radicals [ 45 ]. Moreover, at certain concentrations, ICA has been observed to enhance the viability of TNF-α-induced inflammatory chondrocytes without causing toxicity to cartilage cells, as discovered by Mi et al .…”

Icariin: A Promising Natural Product in Biomedicine and Tissue Engineering

“…ICRN (C 33 H 40 O 15 , M w = 676.67) is a type of prenylated flavonoid, showing extensive bioactivities such as antioxidant [ 44 , 45 , 46 , 47 ], neuroprotective [ 48 , 49 , 50 , 51 , 52 ], and antitumor [ 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 ] behavior as well as anti-inflammatory responses [ 62 , 63 , 64 , 65 , 66 , 67 , 68 ], and can be used to treat erectile dysfunction [ 69 , 70 , 71 , 72 ]. It appears it can improve the function of organs including bones and the heart [ 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 ]. It is crystalline and stable at a low temperature (−20 °C) for approximately two years [ 87 , 88 , 89 , 90 ].…”

GLI family zinc finger protein 2 promotes skin fibroblast proliferation and DNA damage repair by targeting the miR‐200/ataxia telangiectasia mutated axis in diabetic wound healing

“…Shh signaling activation includes interacting with their patched receptor (patched 1), relieving the inhibitive receptor (smoothened frizzled class receptor), and activating the glioma‐associated oncogene homolog (GLI) transcription factor members (such as GLI2) 16 . Decreased GLI2 has also been found in the diabetic animal and high glucose (HG)‐stimulated cell model 17 . Moreover, the Shh protein can promote skin wound healing via the inhibition of the miR‐200 family in embryonic stem cells 18 .…”

“…16 Decreased GLI2 has also been found in the diabetic animal and high glucose (HG)-stimulated cell model. 17 Moreover, the Shh protein can promote skin wound healing via the inhibition of the miR-200 family in embryonic stem cells. 18 Also, from the prediction performed using hTFtarget and the JASPAR database, we found that GLI2 may possess potential binding sites in the promoter region of the miR-200 family.…”