TY - JOUR
T1 - Osthole-loaded N-octyl-O-sulfonyl chitosan micelles (NSC-OST) inhibits RANKL-induced osteoclastogenesis and prevents ovariectomy-induced bone loss in rats
AU - Wang, L.
AU - Zheng, S.
AU - Huang, G.
AU - Sun, J.
AU - Pan, Y.
AU - Si, Y.
AU - Tu, P.
AU - Xu, G.
AU - Ma, Y.
AU - Guo, Y.
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
UR - https://hdl.handle.net/1959.7/uws:66351
U2 - 10.1111/jcmm.15064
DO - 10.1111/jcmm.15064
M3 - Article
SN - 1582-1838
VL - 24
SP - 4105
EP - 4117
JO - Journal of Cellular and Molecular Medicine
JF - Journal of Cellular and Molecular Medicine
IS - 7
ER -