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益生菌促进骨骼生长并挽救 BMP 抑制:研究骨骼健康的新型转基因斑马鱼品系。

Probiotics Enhance Bone Growth and Rescue BMP Inhibition: New Transgenic Zebrafish Lines to Study Bone Health.

机构信息

Department of Life and Environmental Sciences, Università Politecnica delle Marche, Via Brecce Bianche, 60131 Ancona, Italy.

Laboratoire d'Organogenèse et Régénération, GIGA-I3, B34, Université de Liège, 4000 Liège, Belgium.

出版信息

Int J Mol Sci. 2022 Apr 26;23(9):4748. doi: 10.3390/ijms23094748.

Abstract

Zebrafish larvae, especially gene-specific mutants and transgenic lines, are increasingly used to study vertebrate skeletal development and human pathologies such as osteoporosis, osteopetrosis and osteoarthritis. Probiotics have been recognized in recent years as a prophylactic treatment for various bone health issues in humans. Here, we present two new zebrafish transgenic lines containing the coding sequences for fluorescent proteins inserted into the endogenous genes for and with larvae displaying fluorescence in developing osteoblasts and the bone extracellular matrix (mineralized or non-mineralized), respectively. Furthermore, we use these transgenic lines to show that exposure to two different probiotics, and , leads to an increase in osteoblast formation and bone matrix growth and mineralization. Gene expression analysis revealed the effect of the probiotics, particularly , in modulating several skeletal development genes, such as , , and , further supporting their ability to improve bone health. was the more potent probiotic able to significantly reverse the inhibition of bone matrix formation when larvae were exposed to a BMP inhibitor (LDN212854).

摘要

斑马鱼幼虫,特别是基因特异性突变体和转基因系,越来越多地被用于研究脊椎动物骨骼发育和人类病理学,如骨质疏松症、骨质增生症和骨关节炎。近年来,益生菌已被确认为预防人类各种骨骼健康问题的一种方法。在这里,我们介绍了两个新的含有荧光蛋白编码序列的斑马鱼转基因系,这些序列插入了 和 的内源性基因中,幼虫的成骨细胞和骨细胞外基质(矿化或非矿化)中分别显示荧光。此外,我们利用这些转基因系表明,暴露于两种不同的益生菌, 和 ,会导致成骨细胞形成和骨基质生长和矿化增加。基因表达分析显示,益生菌,特别是 ,能够调节几种骨骼发育基因,如 、 、 和 ,进一步支持其改善骨骼健康的能力。 是一种更有效的益生菌,当幼虫暴露于 BMP 抑制剂(LDN212854)时,能够显著逆转骨基质形成的抑制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b698/9102566/4d9bbd89e6e4/ijms-23-04748-g001.jpg

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