Propionibacterium freudenreichii MJ2 inhibits RANKL-induced osteoclast differentiation and ameliorates rheumatoid arthritis in collagen-induced arthritis model

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. 3 samples in triplicate, total 9 samples; negative control, MJ treated group, and SF treated group in raw 264.7 cell