Work

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

Year: 2024

Type: article

Abstract: BackgroundOsteoporosis is a widespread bone disorder that poses a significant public health challenge within the human population.This condition affects a considerable number of individuals across all genders and ethnicities, with its prevalence increasing with advancing age [1].Osteoporosis results from a disruption in bone metabolism, a process that is intricately regulated by osteoblasts and osteoclasts.Current therapeutic options for osteoporosis include bisphosphonates, Raloxifene, Teriparatide, and vitamin D, among others.However, these treatments are accompanied by specific limitations.For instance, the oral administration of bisphosphonates is often associated with gastrointestinal complications, such as gastroesophageal reflux and erosive esophagitis.Furthermore, many of these treatments can lead to the development of hypocalcemia [2].Consequently, there is a pressing need to explore novel targets for the early intervention of osteopenia and to develop new pharmacological agents.It is essential to investigate innovative treatment strategies, particularly those aimed at maintaining balanced bone homeostasis in osteoporosis, with a focus on the utilization of natural substances due to their favorable safety profile.Osteoporosis is a condition that arises from an imbalance between osteoblasts and osteoclasts [3].Osteoclasts, which are multinucleated cells derived from immune cells of the macrophage lineage, play a crucial role in the resorption of osteocytes [4].The differentiation of hematopoietic stem cells (monocytes and macrophages) into multinucleated osteoclasts is a complex multistep process including cell differentiation, migration, fusion, and 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 Auricularia auricula-judae 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 Auricularia auricula-judae extracts.The staining of tartrate-resistant acid phosphatase (TRAP), a marker for osteoclast activity, demonstrated that Auricularia auricula-judae 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.

Source: Journal of Microbiology and Biotechnology

DOI: 10.4014/jmb.2408.08055