Journal
CELLS
Volume 11, Issue 19, Pages -Publisher
MDPI
DOI: 10.3390/cells11193173
Keywords
gut microbiota; chondrocyte senescence; hypertension; captopril
Categories
Funding
- Health and Medical Research Fund Scheme [16172691]
- Research Grants Council of Hong Kong GRF [PolyU15100821M]
- NFSC/RGC schemes [N_PolyU 520/20]
- Hong Kong Polytechnic University Project of Strategic Importance [ZE2C]
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This study investigated the alteration of gut microbiota in a DOCA-induced hypertensive rat model and found that gut microbiota dysbiosis may contribute to chondrocyte senescence induced by DOCA. Captopril can alleviate joint damage and exert its effects by modulating specific bacterial genera levels in the gut microbiota.
Gut microbiota is the key controller of healthy aging. Hypertension and osteoarthritis (OA) are two frequently co-existing age-related pathologies in older adults. Both are associated with gut microbiota dysbiosis. Hereby, we explore gut microbiome alteration in the Deoxycorticosterone acetate (DOCA)-induced hypertensive rat model. Captopril, an anti-hypertensive medicine, was chosen to attenuate joint damage. Knee joints were harvested for radiological and histological examination; meanwhile, fecal samples were collected for 16S rRNA and shotgun sequencing. The 16S rRNA data was annotated using Qiime 2 v2019.10, while metagenomic data was functionally profiled with HUMAnN 2.0 database. Differential abundance analyses were adopted to identify the significant bacterial genera and pathways from the gut microbiota. DOCA-induced hypertension induced p16INK4a+ senescent cells (SnCs) accumulation not only in the aorta and kidney (p < 0.05) but also knee joint, which contributed to articular cartilage degradation and subchondral bone disturbance. Captopril removed the p16INK4a + SnCs from different organs, partially lowered blood pressure, and mitigated cartilage damage. Meanwhile, these alterations were found to associate with the reduction of Escherichia-Shigella levels in the gut microbiome. As such, gut microbiota dysbiosis might emerge as a metabolic link in chondrocyte senescence induced by DOCA-triggered hypertension. The underlying molecular mechanism warrants further investigation.
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