Receptor activator of nuclear factor-κB ligand-mediated osteoclastogenesis signaling pathway and related therapeutic natural compounds

Abstract

Osteoclast is a hematopoietic precursor cell derived from the mononuclear macrophage cell line, which is the only cell with bone resorption function. Its abnormal activation can cause serious osteolysis related diseases such as rheumatoid arthritis, Paget’s disease and osteoporosis. In recent years, the adverse effects caused by anabolic anti-osteolytic drugs have increased the interest of researchers in the potential therapeutic and preventive effects of natural plant derivatives and natural compounds against osteolytic diseases caused by osteoclasts. Natural plant derivatives and natural compounds have become major research hotspots for the treatment of osteolysis-related diseases due to their good safety profile and ability to improve bone. This paper provides an overview of recent advances in the molecular mechanisms of RANKL and downstream signaling pathways in osteoclast differentiation, and briefly outlines potential natural compounds with antiosteoclast activity and molecular mechanisms.

MicroRNA-146a-loaded magnesium silicate nanospheres promote bone regeneration in an inflammatory microenvironment

“…Here, miR-146a potently inhibited in vitro and in vivo osteoclast formation, which may be attributed to the same downregulating effect on TRAF6. 37 , 38 This result suggested the therapeutic potential of MSNs in bone regeneration with an inflammatory microenvironment through regulation of the osteogenesis-osteoclasis balance.…”

Exploring the therapeutic potential of isoorientin in the treatment of osteoporosis: a study using network pharmacology and experimental validation

“…Previous studies have confirmed that abnormal activation of OCs can lead to progressive bone loss, which is the pathological basis of OP, and involves the influence and regulation of multiple signaling pathways (Qu et al 2022a , b ). Representative clinical anti-OP drugs mainly include bisphosphonates, estrogens, and calcitonin.…”

“…This study indicated that ISO has an excellent antioxidant effect and could prevent redox damage to cells through an Nrf2-related mechanism, which has stronger free radical scavenging activity than antioxidants and vitamin C (Brasil et al 2022 ; Yao et al 2012 ). Following appropriate stimulation, a signal transmitted from the cell membrane to the cytoplasm results in the dissociation of Nrf2 from Kelch-like ECH-associated protein 1 (Keap1) and its translocated to the nucleus, where it forms a co-activation complex with small Maf proteins to activate the expression of antioxidant-related genes and products, including CAT, GCLC, and HO-1 (Qu et al 2022a , b ; Yang et al 2022 ). In this study, we demonstrated that ISO dose-dependently inhibited intracellular ROS and suppressed osteoclast differentiation by upregulating the expression of Nrf2, promoting its nuclear translocation, and increasing the expression of related antioxidant enzymes.…”

“…Therefore, identifying safe and effective natural plant derivatives that inhibit the proliferation and differentiation of OCs as anti-OP treatment is important. Numerous studies have demonstrated the therapeutic potential of natural plant derivatives for OP (Nannan et al 2023 ; Nor Muhamad et al 2022 ; Qu et al 2022a , b ).…”

Potato protein hydrolysate inhibits RANKL‐induced osteoclast development by inhibiting osteoclastogenic genes via the NF‐κB/MAPKs signaling pathways

“…5 Consequently, various downstream signaling pathways are activated, including those of nuclear factor kappa B (NF-κB), mitogen-activated protein kinases (MAPK), phospholipase Cγ (PLCγ), and nuclear factor of activated T cells 1 (NFATc1). 6 As a result of transcriptional activation of these receptors consequently increased expression of genes specific to osteoclasts, such as TRAP, osteoclastspecific transmembrane protein (OC-STAMP), osteoclast-associated receptor (OSCAR), dendritic cell-specific transmembrane protein (DC-STAMP), calcitonin receptor (CTR), β3-integrin, ATP6v0d2, and cathepsin K (Ctsk). 7 Moreover, the generation of reactive oxygen species (ROS) induced by RANKL also contributes significantly to the activation of NF-κB and NFATc1, which promote osteoclast differentiation.…”