Abstract
High mobility group box 1 (HMGB1) participates actively in oxidative stress damage and the latter relates closely to diabetic complications, including poor implant osseointegration. This article is aimed at investigating the effects of HMGB1 on dysfunction of bone marrow stromal cells (BMSCs) and impaired osseointegration under diabetic environment. In vitro, BMSCs were treated with normal glucose (NG), high glucose (HG), and HG+glycyrrhizin (HMGB1 inhibitor, HG+GL). Cell proliferation, osteogenic behaviors, and oxidative stress were determined. In vivo, 8-week-old Sprague-Dawley rats were categorized to control, streptozotocin-induced diabetic, and diabetic-GL groups. Rats received GL (50 mg/kg, i.p.) or vehicle treatment daily after titanium implants were planted into the tibiae. After 4 and 8 weeks, plasma lipoperoxide detection, μCT analysis, and histomorphometric evaluation were conducted. By these approaches, we demonstrated that inhibiting HMGB1 by GL significantly attenuated HG-induced upregulation of HMGB1, HMGB1 ligand receptor for advanced glycation end products (RAGE) and their interaction, relieved oxidative stress, and reversed the downregulation of osteogenic markers, resulting in improved osteogenic differentiation. In diabetic rats, GL administration suppressed the upregulation of HMGB1, attenuated the lipoperoxide, and ameliorated the impaired trabecular structure and osseointegration. Taken together, inhibiting HMGB1 can be an effective approach to relieve BMSC dysfunction and enhance osseointegration under diabetic environment.
Highlights
Diabetes mellitus has become a global challenge with its prevalence rate rising at an alarming rate
At 14 d, High mobility group box 1 (HMGB1) mRNA expression reached a 2.88-fold increase in high glucose (HG) group while GL suppressed HMGB1 expression by 63.4%
Western blot analysis showed a further verification to mRNA evaluation, where HMGB1 protein expression reached a 2.05-fold increase in the HG group and GL treatment inhibited its expression to 1.20-fold (Figures 2(b) and 2(c))
Summary
Diabetes mellitus has become a global challenge with its prevalence rate rising at an alarming rate. There is a high prevalence of periodontal disease with resultant tooth loss in diabetic patients [1]. Implant-supported denture is considered to be a favorable treatment to restore lost teeth and rehabilitate occlusion, as long as a reliable osseointegration is achieved between the bone and implant. Dental implant has been described as a safe therapy with a high success rate, diabetes remains a relative contraindication for implant treatment [2] due to its association with oxidative stress [3], delayed wound healing [4], and increased proinflammatory cytokines during osseous healing [5]. Implant in diabetic animals exhibited attenuated bone regeneration capacity and compromised osseointegration [6].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
