Propionibacterium freudenreichii Inhibits RANKL-Induced Osteoclast Differentiation and Ameliorates Rheumatoid Arthritis in Collagen-Induced Arthritis Mice.

Jiah Yeom,Young-Hee Lim,Dong Joon Yim,Seongho Ma

doi:10.3390/microorganisms10010048

Jiah Yeom, Young-Hee Lim + Show 2 more

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https://doi.org/10.3390/microorganisms10010048

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Journal: Microorganisms	Publication Date: Dec 27, 2021
Citations: 9	License type: CC BY 4.0

Affiliation: Korea University, Korea University Medical Center

Abstract

Osteoclast differentiation is crucial for bone absorption, and osteoclasts are involved in bone destruction in rheumatoid arthritis (RA). Dairy Propionibacterium freudenreichii is used as a cheese starter and possesses prebiotic and postbiotic properties. It is known to stimulate the growth of bifidobacteria and produces valuable metabolites, such as vitamin B12 and propionic acid. However, limited information is available on the beneficial effects of P. freudenreichii on human disease. Herein, we aimed to investigate the inhibitory effect of P. freudenreichii MJ2 (MJ2) isolated from raw milk on osteoclast differentiation and evaluate the improvement in RA. The murine macrophage cell line, RAW 264.7, and a collagen-induced arthritis (CIA) mouse model were used to perform in vitro and in vivo studies, respectively. Heat-killed P. freudenreichii MJ2 (hkMJ2)-treated cells significantly inhibited RANKL-induced osteoclast differentiation and TRAP activity. HkMJ2-treated cells exhibited significantly decreased expression of genes and proteins related to RANKL-induced osteoclast differentiation. MJ2 administration decreased the arthritic score in the CIA mouse model. Live and dead MJ2 inhibited bone loss and afforded protection against bone erosion and joint damage in CIA mice. MJ2 decreased the levels of collagen-specific antibodies and inflammatory cytokines and the expression of osteoclast differentiation-related genes and proteins in CIA mice. Interestingly, live and dead MJ2 showed similar RA improvement effects in CIA mice. In conclusion, P. freudenreichii MJ2 inhibited osteoclast differentiation by inhibiting the NF-κB signaling pathway and ameliorated CIA.

Highlights

Publisher’s Note: MDPI stays neutralRheumatoid arthritis (RA) is a common disease that occurs in a large proportion of the global population and affects females more than males [1]
We examined the inhibitory effect of dairy P. freudenreichii MJ2 on osteoclast differentiation and the improvement of collagen-induced arthritis (CIA) in an animal model
RAW 264.7 cells, a murine macrophage cell line, are known to readily differentiate into osteoclast following RANK ligand (RANKL) exposure [31], and RAW 264.7 cells were used to investigate the inhibitory effect of Heat-killed P. freudenreichii MJ2 (hkMJ2) on osteoclast differentiation

Summary

Introduction

Publisher’s Note: MDPI stays neutralRheumatoid arthritis (RA) is a common disease that occurs in a large proportion of the global population and affects females more than males [1]. RA affects other organs, including the eyes, lungs, and heart, and RA-induced chronic inflammation can impact bone absorption and osteolysis [2]. No available drug can completely cure RA. Some drugs such as steroids, nonsteroidal anti-inflammatory drugs (NSAIDs), and disease-modifying anti-rheumatic drugs (DMARDs) can delay the progression of RA or relieve pain and inflammation; patients taking drugs such as aspirin, antidepressants, and antihypertensives might be at a higher risk for additive effects when combined with these drugs. NSAIDs and DMARDs are known to induce side effects, such as liver damage, infection, and induction of tuberculosis [3,4]. The development of effective and safe therapeutic agents is necessary to combat RA

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