(P20-011-23) Lactobacillus rhamnosus Aggravates Bone Loss in a Deoxycorticosterone Acetate (DOCA)-Salt-Induced Osteoporosis Rat Model

Objectives: Probiotics have been shown to harbour preventive and therapeutic effects on osteoporosis due to various mechanisms including increasing calcium absorption and modulating serotonin production via alteration of microbiota. This study aimed to determine if supplementation of live Lactobacillus rhamnosus S1 (LRS1), a local isolated strain, could improve the deterioration of bone loss in DOCA-induced osteoporosis rat model.

Methods: Live LRS1 was used to treat DOCA-salt induced osteoporosis rats. Micro-CT was used to show the bone phenotype and parameters. Immunohistochemical staining showed the expression of CD31 and osterix, the biomarkers for endothelial cells and osteoblast differentiation respectively. Gut microbiota was determined by 16S rRNA sequencing. In cell culture, LRS1 cell-free supernatant (CCS) was added on top of RANKL, an inducer of osteoclastogenic differentiation in macrophage. Expression of markers for osteoclastogenesis and angiogenesis was determined by RT-qPCR. Wound healing assay was done by co-culture of macrophage and bone marrow mesenchymal stem cells (BMSC).

Results: Live LRS1 had no effect on the bone phenotype of healthy rats, yet it aggravated bone loss in DOCA-salt induced osteoporosis rats. The expression of CD31 and osterix had consistent trend as the phenotype of bone loss. The in vitro results showed that LRS1 CCS promoted osteoclastogenesis and angiogenesis. The interaction between the LRS1 CCS and DOCA treatment suppressed the migration of BMSC. Gut microbiota analysis showed that the changes of abundances for g_RF39 and g_Clostridia_UCG-014 had the same trend as the bone loss.

Conclusions: LRS1 aggravated bone loss in DOCA-salt induced rat model. LRS1 suppressed osteoblastogenesis and endothelial cell differentiation in vivo while LRS1 CCS promoted osteoclastogenesis and angiogenesis in cellulo in the DOCA-induced rat and cell model respectively.

Funding Sources: Health and Medical Research Fund No. 15161391, Research Fund Secretariat Health Bureau, Hong Kong