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

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 produ...

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Main Authors: Qi-qi Liu, Wei-wei Wu, Jian Yang, Rui-bin Wang, Ling-ling Yuan, Pei-zhao Peng, Mao-yun Zeng, Ke Yu
Format: Article
Language:English
Published: Wiley 2023-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2023/9330439
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author Qi-qi Liu
Wei-wei Wu
Jian Yang
Rui-bin Wang
Ling-ling Yuan
Pei-zhao Peng
Mao-yun Zeng
Ke Yu
author_facet Qi-qi Liu
Wei-wei Wu
Jian Yang
Rui-bin Wang
Ling-ling Yuan
Pei-zhao Peng
Mao-yun Zeng
Ke Yu
author_sort Qi-qi Liu
collection DOAJ
description 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-κB 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.
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institution Kabale University
issn 1466-1861
language English
publishDate 2023-01-01
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series Mediators of Inflammation
spelling doaj-art-01cfe5bd5507465aad1be8dcdb18a0b02025-02-03T05:57:24ZengWileyMediators of Inflammation1466-18612023-01-01202310.1155/2023/9330439A GP130-Targeting Small Molecule, LMT-28, Reduces LPS-Induced Bone Resorption around Implants in Diabetic Models by Inhibiting IL-6/GP130/JAK2/STAT3 SignalingQi-qi Liu0Wei-wei Wu1Jian Yang2Rui-bin Wang3Ling-ling Yuan4Pei-zhao Peng5Mao-yun Zeng6Ke Yu7The Affiliated Stomatological Hospital of Southwest Medical UniversityThe Affiliated Stomatological Hospital of Southwest Medical UniversityThe Affiliated Stomatological Hospital of Southwest Medical UniversityThe Affiliated Stomatological Hospital of Southwest Medical UniversityThe Affiliated Stomatological Hospital of Southwest Medical UniversityThe Affiliated Stomatological Hospital of Southwest Medical UniversityThe Affiliated Stomatological Hospital of Southwest Medical UniversityThe Affiliated Stomatological Hospital of Southwest Medical UniversityIn 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-κB 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.http://dx.doi.org/10.1155/2023/9330439
spellingShingle Qi-qi Liu
Wei-wei Wu
Jian Yang
Rui-bin Wang
Ling-ling Yuan
Pei-zhao Peng
Mao-yun Zeng
Ke Yu
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
Mediators of Inflammation
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort gp130 targeting small molecule lmt 28 reduces lps induced bone resorption around implants in diabetic models by inhibiting il 6 gp130 jak2 stat3 signaling
url http://dx.doi.org/10.1155/2023/9330439
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