Osthole-loaded N-octyl-O-sulfonyl chitosan micelles (NSC-OST) inhibits RANKL-induced osteoclastogenesis and prevents ovariectomy-induced bone loss in rats.

Lining Wang,Yuhao Si,Yong Ma,Yang Guo,Guicheng Huang,Suyang Zheng,Yalan Pan,Pengcheng Tu,Jie Sun,Guihua Xu

doi:10.1111/jcmm.15064

Lining Wang, Yuhao Si + Show 8 more

Open Access

https://doi.org/10.1111/jcmm.15064

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Abstract

Osthole (OST), a derivative of Fructus Cnidii, has been proved to have potential anti‐osteoporosis effects in our recent studies. However, its pharmacological effects are limited in the human body because of poor solubility and bioavailability. Under the guidance of the classical theory of Chinese medicine, Osthole‐loaded N‐octyl‐O‐sulfonyl chitosan micelles (NSC‐OST), which has not previously been reported in the literature, was synthesized in order to overcome the defects and obtain better efficacy. In this study, we found that NSC‐OST inhibited on the formation and resorption activity of osteoclasts through using a bone marrow macrophage (BMM)‐derived osteoclast culture system in vitro, rather than affecting the viability of cells. We also found that NSC‐OST inhibited osteoclast formation, hydroxyapatite resorption and RANKL‐induced osteoclast marker protein expression. In terms of mechanism, NSC‐OST suppressed the NFATc1 transcriptional activity and the activation of NF‐κB signalling pathway. In vivo, ovariectomized (OVX) rat models were established for further research. We found that NSC‐OST can attenuate bone loss in OVX rats through inhibiting osteoclastogenesis. Consistent with our hypothesis, NSC‐OST is more effective than OST in parts of the results. Taken together, our findings suggest that NSC‐OST can suppress RANKL‐induced osteoclastogenesis and prevents ovariectomy‐induced bone loss in rats and could be considered a safe and more effective anti‐osteoporosis drug than OST.

Highlights

Bone remodelling refers to the physiological process through which the morphology and density of bone tissue change as the biomechanical environment changes
Postmenopausal osteoporosis (PMO) is a systemic skeletal disease caused by an imbalance between bone resorption and bone formation
Compatibility of medicines is the soul of traditional Chinese medicine prescriptions, and compatibility of ‘mutual promotion’ is the most common mode of compatibility in compound prescriptions

Summary

| INTRODUCTION

Bone remodelling refers to the physiological process through which the morphology and density of bone tissue change as the biomechanical environment changes. Our previous study found that, on the one hand, OST stimulated the proliferation and differentiation of osteoblasts by activating the Wnt/β-catenin signalling pathway and causing endoplasmic reticulum stress and that this stimulation eventually promoted new bone formation.[22] On the other hand, OST induced the down-regulation of related transcriptional factors such as NFATc1 by suppressing the NF-κB signalling pathway, thereby inhibiting the differentiation and maturation of OCs.[23] due to its insolubility in water and its poor absorbability, the bioavailability of OST is limited in the body To overcome these issues, our research group employed the concepts of ‘mutual promotion’ and ‘homology of medicine and food’ in traditional Chinese medicine and synthesized NSC-OST (osthole embedded in N-alkyl-O-sulfonyl chitosan), a novel compound that has not previously been reported in the literature. We further examined the anti-osteoporotic effect of NSC-OST in vivo by establishing an ovariectomized rat model of osteoporosis

| MATERIALS AND METHODS

Findings

| DISCUSSION