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一种新型合成代谢化合物 LLP2A-Ale 通过增强骨形成来抑制小鼠牙周骨丢失。

A new anabolic compound, LLP2A-Ale, reserves periodontal bone loss in mice through augmentation of bone formation.

机构信息

Department of Internal Medicine, University of California, Davis Medical Center, 4625 2nd Avenue, Sacramento, CA, 95817, USA.

Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, China.

出版信息

BMC Pharmacol Toxicol. 2020 Nov 13;21(1):76. doi: 10.1186/s40360-020-00454-x.

DOI:10.1186/s40360-020-00454-x
PMID:33187558
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7664094/
Abstract

BACKGROUND

Currently, there are no effective medications to reverse periodontal disease (PD)-induced bone loss. The objective of this study was to test a new anabolic compound, LLP2A-Ale, or with the combination treatment of mesenchymal stromal cell (MSC), in the treatment of bone loss secondary to PD.

METHODS

PD was induced in mice by placing a ligature around the second right molar. At one week after disease induction, the mice were treated with placebo, LLP2A-Ale, MSCs, or combination of LLP2A-Ale + MSCs, and euthanized at week 4.

RESULTS

We found that PD induced alveolar bone loss that was associated with reduced bone formation. LLP2A-Ale alone or in combination with MSCs sustained alveolar bone formation and reversed alveolar bone loss. Additionally, PD alone caused systemic inflammation and increased the circulating levels of G-CSF, IP-10, MIP-1a, and MIP2, which were suppressed by LLP2A-Ale +/- MSCs. LLP2A-Ale +/- MSCs increased bone formation at the peripheral skeletal site (distal femur), which was otherwise suppressed by PD.

CONCLUSION

Our findings indicated that LLP2A-Ale treatment rescued alveolar bone loss caused by PD, primarily by increasing bone formation. LLP2A-Ale also attenuated the circulating levels of a series of inflammatory cytokines and reversed the PD-induced suppression of systemic bone formation.

摘要

背景

目前，尚无有效的药物可以逆转牙周病（PD）引起的骨丢失。本研究旨在测试一种新的合成代谢化合物 LLP2A-Ale，或联合间充质基质细胞（MSC）治疗 PD 引起的骨丢失。

方法

通过在第二右磨牙周围结扎来诱导 PD。在疾病诱导后一周，将小鼠用安慰剂、LLP2A-Ale、MSC 或 LLP2A-Ale+MSC 联合治疗，并在第 4 周处死。

结果

我们发现 PD 诱导牙槽骨丢失，这与骨形成减少有关。单独使用 LLP2A-Ale 或与 MSC 联合使用均可维持牙槽骨形成并逆转牙槽骨丢失。此外，PD 单独引起全身炎症，并增加循环中的 G-CSF、IP-10、MIP-1a 和 MIP2 水平，这些水平被 LLP2A-Ale +/-MSC 抑制。LLP2A-Ale +/-MSC 增加了外周骨骼部位（股骨远端）的骨形成，而 PD 则抑制了该部位的骨形成。

结论

我们的研究结果表明，LLP2A-Ale 治疗可挽救 PD 引起的牙槽骨丢失，主要通过增加骨形成。LLP2A-Ale 还可减轻一系列炎症细胞因子的循环水平，并逆转 PD 诱导的全身骨形成抑制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b3a/7664094/301f27c096aa/40360_2020_454_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b3a/7664094/3bacfa7b241c/40360_2020_454_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b3a/7664094/61da55baff80/40360_2020_454_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b3a/7664094/431e86ca3b13/40360_2020_454_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b3a/7664094/2c209b8ff95c/40360_2020_454_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b3a/7664094/301f27c096aa/40360_2020_454_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b3a/7664094/3bacfa7b241c/40360_2020_454_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b3a/7664094/61da55baff80/40360_2020_454_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b3a/7664094/431e86ca3b13/40360_2020_454_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b3a/7664094/2c209b8ff95c/40360_2020_454_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b3a/7664094/301f27c096aa/40360_2020_454_Fig5_HTML.jpg

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Treatment of experimental periodontitis with chlorhexidine as adjuvant to scaling and root planing.
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