Inhibitory Effect of (2R)-4-(4-hydroxyphenyl)-2-butanol 2-O-β-d-apiofuranosyl-(1→6)-β-d-glucopyranoside on RANKL-Induced Osteoclast Differentiation and ROS Generation in Macrophages

Abstract

In bone homeostasis, bone loss due to excessive osteoclasts and inflammation or osteolysis in the bone formation process cause bone diseases such as osteoporosis. Suppressing the accompanying oxidative stress such as ROS in this process is an important treatment strategy for bone disease. Therefore, in this study, the effect of (2R)-4-(4-hydroxyphenyl)-2-butanol 2-O-β-d-apiofuranosyl-(1→6)-β-d-glucopyranoside (BAG), an arylbutanoid glycoside isolated from Betula platyphylla var. japonica was investigated in RANKL-induced RAW264.7 cells and LPS-stimulated MC3E3-T1 cells. BAG inhibited the activity of TRAP, an important marker of osteoclast differentiation and F-actin ring formation, which has osteospecific structure. In addition, the protein and gene levels were suppressed of integrin β3 and CCL4, which play an important role in the osteoclast-induced bone resorption and migration of osteoclasts, and inhibited the production of ROS and restored the expression of antioxidant enzymes such as SOD and CAT lost by RANKL. The inhibitory effect of BAG on osteoclast differentiation and ROS production appears to be due to the inhibition of MAPKs phosphorylation and NF-κβ translocation, which play a major role in osteoclast differentiation. In addition, BAG inhibited ROS generated by LPS and effectively restores the mineralization of lost osteoblasts, thereby showing the effect of bone formation in the inflammatory situation accompanying bone loss by excessive osteoclasts, suggesting its potential as a new natural product-derived bone disease treatment.

The pathogenesis of post-stroke osteoporosis and the role oxidative stress plays in its development

“…Osteoclast is a type of multinucleated cell derived from the monocyte/macrophage lineage and is the only cell with bone resorption capacity. Oxidative stress can activate the differentiation of osteoclast precursors and increase bone resorption, as shown by the increase in tartrate-resistant acid phosphatase (TRAP) activity in osteoclasts and the increase in bone resorption area on the bone surface ( 66 ). Autophagy is a catabolic process, which removes damaged organelles and some cell molecules including protein aggregates through lysosomal digestion ( 67 ).…”

Advances in the study of traditional Chinese medicine affecting bone metabolism through modulation of oxidative stress

“…The expression of the aforementioned osteoclast-related factors can induce the differentiation of osteoclast precursors into mature OCs and promote the expression of genes associated with osteoclast formation and bone resorption, including tartrate-resistant acid phosphatase (TRAP), cathepsin K (CTSK), and matrix metalloproteinase-9 (MMP-9) (Huang et al, 2017;Wong et al, 2022). Increasing evidence suggests a relationship between oxidative stress and osteoclast formation (Kim et al, 2020). With aging and estrogen deficiency, ROS accumulate in the skeleton (Manolagas, 2010), and excessive ROS production can activate various signaling pathways and increase bone resorption in the body, accelerating bone loss (Kim et al, 2017).…”

Orcinol Glucoside Improves Senile Osteoporosis through Attenuating Oxidative Stress and Autophagy of Osteoclast via Activating Nrf2/Keap1 and mTOR Signaling Pathway

“…Osteoclast, a multinucleated cell derived from the monocyte/macrophage lineage [ 6 ], is the only discovered cell with the capacity of bone resorption [ 7 ]. Oxidative stress activates the differentiation of preosteoclasts and strengthens the bone resorption as demonstrated by increases in the activity of tartrate-resistant acid phosphatase (TRAP) in osteoclasts and the bone resorption area of osteo-surface well [ 8 ]. Autophagy is a catabolic process, through which damaged organelles and some cellular molecules including protein aggregates are removed by lysosomal digestion [ 9 ].…”