1. A GP130-Targeting Small Molecule, LMT-28, Reduces LPS-Induced Bone Resorption around Implants in Diabetic Models by Inhibiting IL-6/GP130/JAK2/STAT3 Signaling.
- Author
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Liu QQ, Wu WW, Yang J, Wang RB, Yuan LL, Peng PZ, Zeng MY, and Yu K
- Subjects
- Animals, Rats, Cytokine Receptor gp130, Glycation End Products, Advanced metabolism, Interleukin-6 metabolism, Janus Kinase 2 metabolism, Lipopolysaccharides, Osteoclasts metabolism, RANK Ligand metabolism, Signal Transduction, X-Ray Microtomography, Bone Resorption metabolism, Diabetes Mellitus, Experimental drug therapy, Diabetes Mellitus, Experimental metabolism, Diabetes Mellitus, Type 2 metabolism, Peri-Implantitis metabolism
- Abstract
In this study, we examined the effect of the GP130-targeting molecule, LMT-28, on lipopolysaccharide- (LPS-) induced bone resorption around implants in diabetic models using in vitro and rat animal experiments. First, LMT-28 was added to osteoblasts stimulated by LPS and advanced glycation end products (AGEs), and nuclear factor- κ B receptor-activating factor ligand (RANKL) and associated pathways were evaluated. Then, LMT-28 was administered by gavage at 0.23 mg/kg once every 5 days for 2 weeks to type 2 diabetic rats with peri-implantitis induced by LPS injection and silk ligature. The expression of IL-6 and RANKL was evaluated by immunohistochemistry, and the bone resorption around implants was evaluated by microcomputed tomography. The results showed that LMT-28 downregulated the expression of RANKL through the JAK2/STAT3 signaling pathway in osteoblasts stimulated by LPS and AGEs, reduced bone resorption around implants with peri-implantitis, decreased the expression of IL-6 and RANKL, and decreased osteoclast activity in type 2 diabetic rats. This study confirmed the ability of LMT-28 to reduce LPS-induced bone resorption around implants in diabetic rats., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2023 Qi-qi Liu et al.)
- Published
- 2023
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