LPL-RH suppresses bone loss in ovariectomised rat models.

Background: Evidence has revealed that oestrogen deprivation-induced osteolysis is microbiota-dependent and can be treated by probiotics. However, the underlying mechanism require further investigation. This study aims to provide additional evidence supporting the use of probiotics as an adjuvant treatment and to explore the pathophysiology of oestrogen-deprived osteolysis.
Methods: Forty-five SD rats were randomly divided into five groups (n = 9). Rats from four groups were ovariectomised and treated with NS, calcium, probiotics, or calcium + probiotics, while one group underwent a sham operation and was treated with NS. The osteometabolic effects were evaluated, and the mechanistic role of the probiotic supplement was explored.
Results: Intragastric administration of Bifidobacterium animalis subsp. lactis LPL-RH (LPL-RH) markedly suppressed osteoclastic activation and bone calcium loss by downregulating TRAP enzymatic activity, the OPG/RANKL ratio, and the downstream signalling pathway RANKL/TRAF6/NF-κB/NFATc1/TRAP in ovariectomised SD rats. LPL-RH also reduced CD4 ⁺ IL-17 A ⁺ T _H 17 cells in the bone marrow, the pro-osteoclastogenic cytokine IL-17 A, pro-inflammatory molecules (LPS), and its binding protein (LBP) in the blood. LPL-RH restored intestinal ZO-1, occludin, claudin 2, claudin 12, and claudin 15, which improved ileal histopathology, reduced ileal oxidative stress, and attenuated the LPS-responsive TLR4/MyD88/NF-κB pathway. Furthermore, 16 S rRNA sequencing revealed that LPL-RH altered the faecal microbiome by reducing the relative abundance of S24-7 at the family level and promoting Prevotella and Bacteroides at the genus level.
Conclusion: Collectively, LPL-RH suppressed osteoclastogenesis and osteolysis by modulating type 17 immunity and gut microbiome.
Competing Interests: Declarations. Ethical approval: The animal experiments in this study were approved by ethical committee of Nanchang Royo Biotech Co., Ltd (Nanchang, P. R. China) (No. RYE2021110801). All animal experiments were conducted with minimal pain to follow Guide for the Care and Use of Laboratory Animals (NIH, USA). Consent for publication: All authors were consent for the publication of this article. Clinical trial number: Not applicable. Competing interests: The authors declare no competing interests.
(© 2024. The Author(s).)