Department of Life and Environmental Sciences, Università Politecnica Delle Marche, Via Brecce Bianche, 60131, Ancona, Italy.
Biostructures and Biosystems National Institute-Interuniversity Consortium, Viale delle Medaglie d'Oro 305, 00136, Rome, Italy.
Sci Rep. 2022 May 16;12(1):8057. doi: 10.1038/s41598-022-12138-z.
Probiotics are live microorganisms that confer several beneficial effects to the host, including enhancement of bone mineralization. However, probiotic action on bone regeneration is not well studied and therefore we analysed various effects of probiotic treatment on the caudal fin regeneration of zebrafish. Morphological analysis revealed an increased regenerated area with shorter and thicker lepidotrichia segments after probiotic treatment. Fourier transform infrared spectroscopy imaging analysis highlighted the distribution of phosphate groups in the regenerated fins and probiotic group showed higher amounts of well-crystallized hydroxyapatite. At the midpoint (5 days post amputation) of regeneration, probiotics were able to modulate various stages of osteoblast differentiation as confirmed by the upregulation of some key marker genes such as runx2b, sp7, col10a1a, spp1 and bglap, besides suppressing osteoclast activity as evidenced from the downregulation of ctsk. Probiotics also caused an enhanced cell cycle by regulating the expression of genes involved in Retinoic acid (rarga, cyp26b1) and Wnt/β-catenin (ctnnb1, ccnd1, axin2, sost) signaling pathways, and also modulated phosphate homeostasis by increasing the entpd5a levels. These findings provide new outlooks for the use of probiotics as a prophylactic treatment in accelerating bone regeneration and improving skeletal health in both aquaculture and biomedical fields.
益生菌是对宿主有多种有益作用的活体微生物，包括增强骨矿化。然而，益生菌对骨再生的作用尚未得到充分研究，因此我们分析了益生菌处理对斑马鱼尾鳍再生的各种影响。形态分析显示，益生菌处理后再生区域增大，表皮刺段变短变厚。傅里叶变换红外光谱成像分析突出了再生鳍中磷酸盐基团的分布，益生菌组显示出更多结晶良好的羟基磷灰石。在再生的中点（截肢后 5 天），益生菌能够调节成骨细胞分化的各个阶段，这一点得到了一些关键标记基因如 runx2b、sp7、col10a1a、spp1 和 bglap 的上调的证实，此外还抑制破骨细胞活性，这一点从 ctsk 的下调得到了证明。益生菌还通过调节参与视黄酸（rarga、cyp26b1）和 Wnt/β-catenin（ctnnb1、ccnd1、axin2、sost）信号通路的基因表达来增强细胞周期，还通过增加 entpd5a 水平来调节磷酸盐稳态。这些发现为益生菌作为一种预防治疗方法在水产养殖和生物医学领域加速骨再生和改善骨骼健康提供了新的思路。
