Abstract
Nitidine chloride (NC), a bioactive alkaloid isolated from Zanthoxylum nitidum, has been used as a herbal ingredient in toothpaste that prevents cavities for decades. It also displays potential antitumor and anti-inflammation properties. However, its anticatabolic effect on bone is not known. We investigated the effect of NC on osteoclastogenesis, bone resorption and RANKL-induced NF-κB and NFATc1 signalling. In mouse-derived bone marrow monocytes (BMMs), NC suppressed RANKL-induced multinucleated tartrate-resistant acid phosphatase (TRAP)-positive osteoclast formation and bone resorption in a dose dependent manner. NC attenuated the expression of osteoclast marker genes including cathepsin K, D2, calcitonin receptor, NFATc1, and TRAP. Further, NC inhibited RANKL-activated NF-κB and NFATc1 signalling pathways. In vivo study revealed that NC abrogated oestrogen deficiency-induced bone loss in ovariectomized mice. Histological analysis showed that the number of osteoclasts was significantly lower in NC-treated groups. Collectively, our data demonstrate that NC suppressed osteoclastogenesis and prevented OVX-induced bone loss by inhibiting RANKL-induced NF-κB and NFATc1 signalling pathways. NC may be a natural and novel treatment for osteoclast-related bone lytic diseases.
Highlights
Bone is a dynamic tissue constantly undergoing remodelling by two opposite forces, namely bone formation by osteoblasts and bone resorption by osteoclasts
These results suggest that Nitidine chloride (NC) dose-dependently inhibits RANKL-induced osteoclastogenesis in bone marrow monocytes (BMMs) cells
We report that NC inhibits osteoclast differentiation and bone resorption
Summary
Bone is a dynamic tissue constantly undergoing remodelling by two opposite forces, namely bone formation by osteoblasts and bone resorption by osteoclasts. Targeting RANKL-activated downstream signalling pathways is a promising strategy to inhibit excessive bone resorption, thereby alleviating bone loss. NC exerted its anti-inflammatory effects by modulating MAPK and NF-κB pathways and subsequently suppressing lipopolysaccharide (LPS)-induced TNF-α, IL-1β, and IL-6 production in RAW 264.7 cells[10]. We found that NC dose dependently suppressed RANKL-induced osteoclast differentiation and osteoclastic bone resorption. To further examine the physiological relevance of NC’s inhibitory effect on osteoclastogenesis and bone resorption, we used an OVX mouse model to examine whether NC had a preventative effect on oestrogen deficiency-induced bone loss in vivo. In line with our in vitro results, NC treatment significantly prevented OVX induced bone loss and abrogated excessive osteoclast formation. Our data clearly show that NC suppresses osteoclastogenesis and osteoclastic bone resorbing activity through inhibition of RANKL-induced NF-κB and NFAT signalling pathways
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