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丁酸钠通过抑制 smad1 表达抑制人牙周膜干细胞成骨分化。

Sodium butyrate inhibits osteogenesis in human periodontal ligament stem cells by suppressing smad1 expression.

机构信息

Department of Orthodontics, School of Stomatology, Capital Medical University, Tian Tan Xi Li No.4, Beijing, 100050, People's Republic of China.

Laboratory of Tissue Regeneration and Immunology and Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Beijing, People's Republic of China.

出版信息

BMC Oral Health. 2022 Jul 19;22(1):301. doi: 10.1186/s12903-022-02255-6.

DOI:10.1186/s12903-022-02255-6
PMID:35854293
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9297574/
Abstract

BACKGROUND

Butyrate is a major subgingival microbial metabolite that is closely related to periodontal disease. It affects the proliferation and differentiation of mesenchymal stem cells. However, the mechanisms by which butyrate affects the osteogenic differentiation of periodontal ligament stem cells (PDLSCs) remain unclear. Here, we investigated the effect of sodium butyrate (NaB) on the osteogenic differentiation of human PDLSCs.

METHODS

PDLSCs were isolated from human periodontal ligaments and treated with various concentrations of NaB in vitro. The cell counting kit-8 assay and flow cytometric analysis were used to assess cell viability. The osteogenic differentiation capabilities of PDLSCs were evaluated using the alkaline phosphatase activity assay, alizarin red staining, RT-PCR, western blotting and in vivo transplantation.

RESULTS

NaB decreased PDLSC proliferation and induced apoptosis in a dose- and time-depend manner. Additionally, 1 mM NaB reduced alkaline phosphatase activity, mineralization ability, and the expression of osteogenic differentiation-related genes and proteins. Treatment with a free fatty acids receptor 2 (FFAR2) antagonist and agonist indicated that NaB inhibited the osteogenic differentiation capacity of PDLSCs by affecting the expression of Smad1.

CONCLUSION

Our findings suggest that NaB inhibits the osteogenic differentiation of PDLSCs by activating FFAR2 and decreasing the expression of Smad1.

摘要

背景

丁酸盐是一种与牙周病密切相关的主要龈下微生物代谢产物。它影响间充质干细胞的增殖和分化。然而,丁酸盐影响牙周韧带干细胞(PDLSCs)成骨分化的机制尚不清楚。在这里,我们研究了丁酸钠(NaB)对人牙周韧带干细胞(PDLSCs)成骨分化的影响。

方法

从人牙周韧带中分离出 PDLSCs,并在体外用不同浓度的 NaB 处理。细胞计数试剂盒-8 检测和流式细胞术分析用于评估细胞活力。通过碱性磷酸酶活性测定、茜素红染色、RT-PCR、western blot 和体内移植评估 PDLSCs 的成骨分化能力。

结果

NaB 呈剂量和时间依赖性地降低 PDLSC 增殖并诱导细胞凋亡。此外,1 mM NaB 降低碱性磷酸酶活性、矿化能力以及成骨分化相关基因和蛋白的表达。用游离脂肪酸受体 2(FFAR2)拮抗剂和激动剂处理表明,NaB 通过影响 Smad1 的表达来抑制 PDLSCs 的成骨分化能力。

结论

我们的研究结果表明,NaB 通过激活 FFAR2 和降低 Smad1 的表达来抑制 PDLSCs 的成骨分化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81db/9297574/b17cd494e837/12903_2022_2255_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81db/9297574/067d64d0a251/12903_2022_2255_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81db/9297574/ab72c9f075cf/12903_2022_2255_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81db/9297574/d1a995cc8fde/12903_2022_2255_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81db/9297574/8019037026ad/12903_2022_2255_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81db/9297574/b17cd494e837/12903_2022_2255_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81db/9297574/067d64d0a251/12903_2022_2255_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81db/9297574/ab72c9f075cf/12903_2022_2255_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81db/9297574/d1a995cc8fde/12903_2022_2255_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81db/9297574/8019037026ad/12903_2022_2255_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81db/9297574/b17cd494e837/12903_2022_2255_Fig5_HTML.jpg

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