Silibinin-modified Hydroxyapatite coating promotes the osseointegration of titanium rods by activation SIRT1/SOD2 signaling pathway in diabetic rats

Abstract

The purpose of this study is to investigate the role of Silibinin (SIL)-modified Hydroxyapatite coating on osseointegration in diabetes in vivo and in vitro and explore the mechanism of osteogenic differentiation of MC3T3-E1. RT-qPCR, Immunofluorescence, and Western blot were used to measure the expression level of oxidative Stress Indicators and osteogenic markers proteins. Moreover, CCK-8 assay was conducted to detect cell viability in hyperglycemia. Alizarin red staining and alkaline phosphatase staining were used to examine osteogenic function and calcium deposits. The diabetic rat model receive titanium rod implantation was set up successfully and Von-Gieson staining was used to examine femoral bone tissue around titanium rod. Our results showed that intracellular oxidative stress in hyperglycemia was overexpressed, while FoxO1, SIRT1, GPX1, and SOD2 were downregulated. SIL suppressed oxidative stress to promote osteogenic differentiation. Additionally, it was confirmed that SIL promoted osteogenic differentiation of MC3T3-E1 and obviously restored the osseointegration ability of diabetic rats. Further study indicated that SIL exerted its beneficial function through activation SIRT1/SOD2 signaling pathway to restore osteoblast function, and improved the osseointegration and stability of titanium rods in vivo. Our research suggested that the SIL-modulated oxidative Stress inhibition is responsible for the activation of the process of osteogenic differentiation through activation SIRT1/SOD2 signaling pathway in hyperglycemia, providing a novel insight into improving prosthetic osseointegration in diabetic patients.

Favorable osteogenic activity of vericiguat doped in β-tricalcium phosphate: In vitro and in vivo studies

“…44 SOD2 is one of the most important antioxidant enzymes in the body, and it is primarily responsible for neutralizing superoxide radicals, which are highly reactive and can cause significant damage to cells and tissues. 26,45 Hence, in this investigation, we further explored the influence of VIT on the differentiation of osteoblasts when exposed to increased levels of oxidative stress. As expected, VIT displayed a safeguarding effect on osteoblast differentiation due to its antioxidant characteristics.…”

Activation of PGC‐1α‐dependent mitochondrial biogenesis supports therapeutic effects of silibinin against type I diabetic periodontitis

“…Despite the beneficial effect of the systemic administration of silibinin, local delivery of drugs is preferable to systemic application for periodontal treatment due to its relative safety and immediate effects at the action site (Wei et al, 2021). Silibinin has been locally made into coating that greatly enhanced bone regeneration (Tao et al, 2022). Furthermore, silibinin has been developed as injectable, biodegradable hydrogels (Cho et al, 2012), which might be an efficient delivery system for silibinin in treating DP.…”

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

“…After a week, rats with random blood glucose concentration higher than 250 mg/dL (13.89 mmol/L) could be defined as T1DM. Referring to the methods of Tao et al, we maintained the diet for 90 days to study the effects of diabetes on bone [ 17 ].…”

“…Seminal discoveries have deconstructed the bone microenvironment into a unique niche composed of multiple cellular and extracellular components and shown the devastating influence of the diabetic microenvironment on bone metabolism [ 16 ]. Osteoblasts play a central role in bone formation, while ROS also reduce osteoblast activity and functional response [ 17 ]. Ma et al found that ROS accumulation in type 2 diabetes led to mitochondrial dysfunction and ferroptosis in osteoblasts [ 18 ].…”