SHORT CHAIN FATTY ACIDS MITIGATE OSTEOCLAST-MEDIATED ARTHRITIC BONE REMODELLING
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1006076 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25658776_1.fastq.gz | Fastqsanger.gz | |||
| SRR25658776_2.fastq.gz | Fastqsanger.gz | |||
| SRR25658777_1.fastq.gz | Fastqsanger.gz | |||
| SRR25658777_2.fastq.gz | Fastqsanger.gz | |||
| SRR25658778_1.fastq.gz | Fastqsanger.gz |
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Project description:Osteoclast differentiation is crucial for bone absorption and osteoclast is involved in bone destruction in rheumatoid arthritis. The aim of this study was to investigate the inhibitory effect of MJ2 on osteoclast differentiation and to elucidate its mechanism. Murine macrophage cell line, Raw 264.7 cells and collagen-induced arthritis mouse model were used for in vitro and in vivo study, respectively. MJ2-treated cells significantly inhibited osteoclast differentiation and decreased arthritic score. Surface proteins (SP) extracted from MJ2 also showed inhibitory effect on osteoclast differentiation by upregulating lipocalin 2 (lcn2) expression. Specifically, heat shock protein 60 (hsp60) in SP was revealed as an active component of MJ2. Hsp60 inhibited binding of receptor activator of nuclear factor-κB ligand (RANKL) to receptor activator of nuclear factor κB (RANK). In conclusion, MJ2 inhibited osteoclast formation and differentiation through lcn2 and RANKL-binding property and the effective component of MJ2 might be hsp60 present in surface layer.
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Project description:Although oral antibiotics can predispose to joint inflammation, this phenomenon remains poorly understood. Here, we leverage mouse models of alphavirus arthritis to investigate the gut commensals, metabolites, and host mechanisms that promote musculoskeletal inflammation. Mice treated with a short course of oral antibiotics exhibited worsened arthritis after chikungunya virus (CHIKV) infection. This phenotype was associated with loss of short chain fatty acids (SCFA) and greater intestinal permeability, and required TLR4 signaling, MyD88 expression, monocytes, antigen-specific and bystander CD4+ T cells, and pro-inflammatory cytokines. Administration of exogenous SCFA or colonization of mice with bacterial species that generate SCFA mitigated CHIKV-induced joint inflammation. Single cell RNA sequencing revealed that gut-derived SCFA restrain the inflammatory phenotype of synovial CD4+ T cells and limit activation of monocytes and osteoclast-like cells. Thus, antibiotic-triggered gut dysbiosis exacerbates alphavirus arthritis by shaping the inflammatory profile of both infiltrating and resident immune cells in joint tissues.
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