Kim Inwook, Park Sankyu, Kim Jieun, Park So Young, Seo Jeongmin, Roh Sangho
Biomedical Research Institute, NeoRegen Biotech Co., Ltd., Seocho-gu 06663, Republic of Korea.
Biomedical Research Institute, NeoRegen Biotech Co., Ltd., Seocho-gu 06663, Republic of Korea; Cellular Reprogramming and Embryo Biotechnology Laboratory, Dental Research Institute, Seoul National University School of Dentistry, Seoul 08826, Republic of Korea.
Biomed Pharmacother. 2025 Mar;184:117913. doi: 10.1016/j.biopha.2025.117913. Epub 2025 Feb 16.
Bone-related diseases such as osteoporosis pose a significant health economic burden to countries around the world and, because current treatments are insufficient, more effective therapies are desperately needed. This study explored the potential of Lactobacillus paracasei L30 extract to influence the osteogenic differentiation of human bone marrow mesenchymal stem cells (hBM-MSCs). Our results showed that L30 extract significantly enhanced the expression of osteogenic markers in hBM-MSCs, including alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2), and collagen type I alpha 1 (COL1A1). Mechanistic studies revealed that L30 extract activated the p38 MAPK and AKT signaling pathways, leading to phosphorylation of Glycogen synthase kinase-3 beta (GSK3β) and subsequent nuclear translocation of β-catenin. Conversely, inhibition of p38 MAPK, AKT, or knockdown of β-catenin significantly attenuated the osteogenic effects of L30 extract on hBM-MSCs. Furthermore, we found that L30 extract promoted osteogenic differentiation in primary osteoblast precursors isolated from mouse calvaria and enhances bone formation in ex vivo calvarial organ cultures. Therefore, the application of Lactobacillus paracasei L30 extract in such contexts could serve as a therapeutic approach for promoting bone formation. Collectively, our findings suggest a novel approach for the clinical management of bone-related disorders, with possible applications for treating diseases such as osteoporosis.
骨质疏松症等骨相关疾病给世界各国带来了巨大的健康经济负担,而且由于目前的治疗方法并不充分,因此迫切需要更有效的治疗方法。本研究探讨了副干酪乳杆菌L30提取物影响人骨髓间充质干细胞(hBM-MSCs)成骨分化的潜力。我们的结果表明,L30提取物显著增强了hBM-MSCs中成骨标志物的表达,包括碱性磷酸酶(ALP)、 runt相关转录因子2(RUNX2)和I型胶原α1(COL1A1)。机制研究表明,L30提取物激活了p38 MAPK和AKT信号通路,导致糖原合酶激酶-3β(GSK3β)磷酸化,随后β-连环蛋白发生核转位。相反,抑制p38 MAPK、AKT或敲低β-连环蛋白可显著减弱L30提取物对hBM-MSCs的成骨作用。此外,我们发现L30提取物促进了从小鼠颅骨分离的原代成骨细胞前体细胞的成骨分化,并增强了离体颅骨器官培养中的骨形成。因此,在这种情况下应用副干酪乳杆菌L30提取物可作为促进骨形成的一种治疗方法。总的来说,我们的研究结果为骨相关疾病的临床管理提出了一种新方法,可能适用于治疗骨质疏松症等疾病。