Dual effects of baicalin on osteoclast differentiation and bone resorption

Abstract

Osteoclasts (OC) are critical cells responsible for many bone diseases such as osteoporosis. It is of great interest to identify agents that can regulate the activity of OC to treat osteolytic bone diseases. In this study, we found that baicalin exerted a two‐way regulatory effect on OC in a concentration‐dependent manner in vitro and in vivo. In detail, baicalin at a low concentration (below 1 μmol/L) enhanced OC differentiation and bone resorption, but baicalin at a high concentration (above 2 μmol/L) exhibited inhibitory effects on OC. We demonstrated that baicalin at low concentrations enhanced the mitogen‐activated protein kinase (MAPK) (ERK) signalling pathway and activated c‐Fos and NFATc1 expression, and thus enhanced gene expression, OC differentiation and bone resorption. However, baicalin at higher levels not only suppressed ERK phosphorylation and c‐fos and NFATc1 expression, but also altered the expression of apoptosis‐related proteins, and therefore inhibiting OC function. This dual effect was further verified in an LPS‐induced mouse calvarial osteolysis model, evidenced by enhanced osteolysis at a lower concentration but reduced bone loss at a higher concentration. Overall, our findings indicate that baicalin exerts dose‐dependent effects on OC formation and function. Therefore, caution should be applied when using baicalin to treating OC‐related bone diseases.

Quercetin inhibits macrophage polarization through the p‐38α/β signalling pathway and regulates OPG/RANKL balance in a mouse skull model

“…3,4 Previous researchers have focused on the pathological mechanisms of osteoclasts formation. [5][6][7][8] However, few studies have shown the increased accumulation of macrophages at the beginning of wear particles. The macrophage cells are then further differentiated into osteoclasts with bone resorptive function.…”

Anti-Osteoporosis Effect of Perilla frutescens Leaf Hexane Fraction through Regulating Osteoclast and Osteoblast Differentiation

“…Luteolin also suppresses the mitochondrial apoptosis of osteoblasts via inhibition of STAT1 activity [ 73 ]. Moreover, baicalin was shown to be therapeutic for osteoclast-related bone diseases through the inhibition of the NF-κB and ERK pathways [ 74 ]. Baicalein can stimulate osteoblast differentiation via the activation of the mTORC1 signaling pathways, including the P-S6K1 and P-4E/BP1 transcription factors [ 75 ].…”

Shuxuetong injection simultaneously ameliorates dexamethasone‑driven vascular calcification and osteoporosis

“…There are two sclerostin inhibitors, romosozumab and baicalin; romosozumab is a human monoclonal antibody against sclerostin (45), and baicalin, a herb-derived flavonoid compound, binds to sclerostin via hydrophobic interactions with the amino acid residues on loop2 region, but outside the Pro-Asn-Ala-Ile-Gly motif, particularly the Arg-Gly-Lys-Trp-Trp-Arg motif (46). The beneficial effects of these two agents against osteoporosis have been reported in a number of studies (47)(48)(49)(50). Although the effect of romosozumab on cardiovascular events including VC is controversial (45,51), baicalin has been reported to relax VSMCs (52), ameliorate atherosclerosis (53), prevent trans-differentiation of VSMCs (54) and inhibit vascular remodeling (55), via which baicalin may ameliorate VC.…”