The Biphasic Activity of Auricularia Auricula-Judae Extract on Bone Homeostasis through Inhibition of Osteoclastogenesis and Modulation of Osteogenic Activity

Osteoporosis arises from the disturbance of bone homeostasis, a process regulated by osteoblasts and osteoclasts. The treatment and prevention of bone metabolic disorders resulting from an imbalance in bone homeostasis require the use of agents that effectively promote both bone formation and anti-resorptive effects. Therefore, an investigation was carried out to determine the potential of the edible mushroom <i>Auricularia auricula-judae</i> in modulating bone remodeling by inhibiting RANKL-induced osteoclastogenesis and enhancing BMP-2-stimulated osteoblast differentiation. Moreover, this study assessed the mode of action of the <i>Auricularia auricula-judae</i> extracts. The staining of tartrate-resistant acid phosphatase (TRAP), a marker for osteoclast activity, demonstrated that <i>Auricularia auricula-judae</i> water extract (AAJWE) inhibited the formation of multinucleated osteoclasts while exhibiting no cytotoxic effects. The study demonstrated that AAJWE reduced RANKL-induced osteoclast differentiation by inhibiting c-Fos/NFATc1 through the inhibition of ERK and JNK phosphorylation during the RANKL-induced osteoclast differentiation. Moreover, AAJWE exhibited a dose-dependent induction of ALP expression in the presence of BMP-2 during osteoblast differentiation. The AAJWE strengthened BMP-2-induced osteogenesis through the activation of Runx2 and Smad phosphorylation. Therefore, AAJWE emerges as a promising candidate for both prevention and therapy owing to its biphasic effect, which aids in the preservation of bone homeostasis.