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LP45抑制RANKL/OPG信号通路并预防糖皮质激素诱导的骨质疏松症。

LP45 inhibits the RANKL/OPG signaling pathway and prevents glucocorticoid-induced osteoporosis.

作者信息

Jiang Xiaofeng, Qi Xiaojun, Xie Chao

机构信息

Department of Joint Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China.

Department of Spine Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China.

出版信息

Food Nutr Res. 2023 Mar 24;67. doi: 10.29219/fnr.v67.9064. eCollection 2023.

DOI:10.29219/fnr.v67.9064
PMID:37056702
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10087339/
Abstract

OBJECTIVE

To examine the potential effect of the probiotic strain LP45 on osteoporosis and to explore the involved molecular mechanisms.

METHODS

A rat model of glucocorticoid-induced osteoporosis (GIO) was established, which was also orally administered with increasing doses of LP45 for 8 weeks. After the termination of the 8-week treatment, the tibia and femur bones of rats were analyzed for bone histomorphometry, bone mineral content (BMC), and bone mineral density (BMD). Femoral biomechanics were assessed. In addition, levels of osteocalcin, tartrate-resistant acid phosphatase 5 (TRAP5), osteoprotegerin (OPG), and receptor activator of nuclear factor kappa-B ligand (RANKL) in the serum and bone marrow were also measured using ELISA, Western blot, and real time-polymerase chain reaction.

RESULTS

GIO caused obvious defects in tibia and femur bone structures, in terms of tissue/bone volume, trabecular separation, trabecular thickness, and trabecular number, which could be rescued by LP45 dose dependently. The GIO-induced reductions in BMC, BMD, osteoblast surfaces per bone surface (BS), as well as elevated osteoclast surface per BS were largely restored by LP45 administration dose-dependently. LP45 also increased femoral biomechanics of GIO rats. Importantly, LP45 dose-dependently restored the changes of osteocalcin, TRAP5, OPG, and RANKL in the serum as well as bone marrow of GIO rats.

CONCLUSION

Oral LP45 administration could significantly prevent bone defects in GIO rats, suggesting its potential as a dietary supplement with beneficial effects against osteoporosis, which might involve the RANKL/OPG signaling pathway.

摘要

目的

研究益生菌菌株LP45对骨质疏松症的潜在影响,并探讨其相关分子机制。

方法

建立糖皮质激素诱导的骨质疏松症(GIO)大鼠模型,同时对其口服递增剂量的LP45,持续8周。在8周治疗结束后,对大鼠的胫骨和股骨进行骨组织形态计量学、骨矿物质含量(BMC)和骨矿物质密度(BMD)分析。评估股骨生物力学性能。此外,还采用酶联免疫吸附测定(ELISA)、蛋白质免疫印迹法(Western blot)和实时聚合酶链反应,测量血清和骨髓中骨钙素、抗酒石酸酸性磷酸酶5(TRAP5)、骨保护素(OPG)和核因子κB受体活化因子配体(RANKL)的水平。

结果

GIO导致胫骨和股骨的骨结构在组织/骨体积、小梁间距、小梁厚度和小梁数量方面出现明显缺陷,而LP45可剂量依赖性地挽救这些缺陷。LP45给药后,GIO诱导的BMC、BMD、每骨表面成骨细胞表面(BS)减少以及每BS破骨细胞表面增加,在很大程度上得到剂量依赖性恢复。LP45还增加了GIO大鼠的股骨生物力学性能。重要的是,LP45剂量依赖性地恢复了GIO大鼠血清和骨髓中骨钙素、TRAP5、OPG和RANKL的变化。

结论

口服LP45可显著预防GIO大鼠的骨缺陷,表明其作为具有抗骨质疏松有益作用的膳食补充剂的潜力,这可能涉及RANKL/OPG信号通路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1b1/10087339/b24f896f8e1c/FNR-67-9064-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1b1/10087339/c97ae5170280/FNR-67-9064-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1b1/10087339/3dd06488cd86/FNR-67-9064-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1b1/10087339/f0f60ba89bce/FNR-67-9064-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1b1/10087339/b24f896f8e1c/FNR-67-9064-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1b1/10087339/c97ae5170280/FNR-67-9064-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1b1/10087339/3dd06488cd86/FNR-67-9064-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1b1/10087339/f0f60ba89bce/FNR-67-9064-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1b1/10087339/b24f896f8e1c/FNR-67-9064-g004.jpg

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