Purple tea water extract blocks RANKL-induced osteoclastogenesis through modulation of Akt/GSK3β and Blimp1-Irf8 pathways

Abstract

A number of studies demonstrated that some tea extracts exert inhibitory effects on osteoclastogenesis induced by receptor activator of nuclear factor κB ligand (RANKL). However, the effect of purple tea,...

Myrislignan Targets Extracellular Signal-regulated Kinase (ERK) and Modulates Mitochondrial Function to Dampen Osteoclastogenesis and Ovariectomy-i nduced Osteoporosis

“…Bone health is strictly regulated, while osteoporosis occurs mainly due to the disruption of bone homeostasis, which depends on the balance between osteoclastic bone resorption and osteoblastic bone formation (2,5). As the only specialized multinucleated cells derived from the mononuclear macrophage lineage in vivo (6), osteoclasts could be activated under the stimulation of various pathological factors (7) (chronic use of drugs, immobilization, malnutrition, and chronic in ammation) to accelerate bone resorption (8, 9), leading to osteoporosis and osteoporosis-related diseases, including Alzheimer's disease, diabetes and cancers and so on (10,11). Therefore, inhibiting the formation and activity of osteoclasts is a crucial strategy for treating osteoporosis.…”

“…After the fusion of primary bone marrow-derived macrophages mononuclear pre-osteoclasts, they form multinuclear osteoclasts (10). There are two indispensable receptors expressing in pre-osteoclast cell surfaces -colony stimulating factor-1 receptor (c-Fms) and receptor activator of nuclear factor κB (RANK) (6, 10).…”

“…The binding of c-Fms and macrophage colony-stimulating factor (M-CSF) bene ts preosteoclasts and osteoclasts' subsequent survival and proliferation (6, 8). The induction of osteoclast differentiation is in connection with the binding of RANK to RANKL (7,10). And then, RANKL/RANK signaling gives rise to the collection of TNF receptor-associated factor 6 (TRAF6) (9), inducing the mobilization of several subsequent pathways, such as mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) pathways (11,21), which are classical pathways related to osteoclast differentiation (10).…”

“…The induction of osteoclast differentiation is in connection with the binding of RANK to RANKL (7,10). And then, RANKL/RANK signaling gives rise to the collection of TNF receptor-associated factor 6 (TRAF6) (9), inducing the mobilization of several subsequent pathways, such as mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) pathways (11,21), which are classical pathways related to osteoclast differentiation (10). NFATc1, the critical osteoclastogenesis-controlling master transcription factor, is subsequently initiated to express by RANKL (10).…”

“…And then, RANKL/RANK signaling gives rise to the collection of TNF receptor-associated factor 6 (TRAF6) (9), inducing the mobilization of several subsequent pathways, such as mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) pathways (11,21), which are classical pathways related to osteoclast differentiation (10). NFATc1, the critical osteoclastogenesis-controlling master transcription factor, is subsequently initiated to express by RANKL (10). Eventually, transcription factor NFATc1 induces the expression of genes encoding osteoclast-relevant proteins, including TRAP, cathepsin K (CTSK), ATPase H + transporting v0 subunit d2 (Atp6v0d2) (6,22), matrix metalloproteinase (Mmp9) (6) and dendritic cellspeci c transmembrane protein (Dcstamp) (10), which promote osteoclast formation and then lead to bone resorption.…”