Xing-Min Wang1, Hui Liu2, Jian-Yu Li1,3,4, Jin-Xia Wei1, Xia Li1, Yong-Liang Zhang1,3, Ling-Zhi Li1,3, Xi-Zheng Zhang4,5. 1. Department of Pharmacy, Logistics University of Chinese People's Armed Police Forces, Tianjin, China. 2. Key Laboratory of Artificial Cell, Artificial Cell Engineering Technology Research Center of Public Health Ministry, Tianjin Third Central Hospital, Nankai University, Tianjin, China. 3. Key Laboratory for Prevention and Control of Occupational and Environmental Hazard, Tianjin, China. 4. Key Laboratory of Interforce Functionality and Personalization of Bone Implants, Tianjin, China. 5. Institute of Medical Equipment, Academy of Military Medical Sciences, Tianjin, China.
Abstract
Wang, Xing-Min, Hui Liu, Jian-Yu Li, Jin-Xia Wei, Xia Li, Yong-Liang Zhang, Ling-Zhi Li, and Xi-Zheng Zhang. Rosamultin attenuates acute hypobaric hypoxia-induced bone injuries by regulation of sclerostin and its downstream signals. High Alt Med Biol. 21:273-286, 2020. Background: Rosamultin, one of the compounds extracted from Potentilla anserina L., exhibited significant pharmacological activity against oxidative stress and hypoxic injury in our previous study. However, the effect of rosamultin on bone damage induced by acute hypobaric hypoxia (HH) has not been thoroughly studied. Methods: In this study, we first investigated the protective effect of rosamultin against bone damage in rats following acute exposure to simulated high-altitude hypoxia. Furthermore, we explored the detailed mechanism involved in the regulation of rat bone remodeling by rosamultin in an acute HH environment through analysis of sclerostin expression and the regulation of downstream signaling pathways. Results: Pretreatment with rosamultin significantly reduced HH-induced oxidative stress and inflammation, improved bone metabolic abnormalities, and alleviated the imbalance in bone remodeling in rats exposed to acute HH. Rosamultin markedly downregulated the expression of sclerostin, activated the Wnt/β-catenin signaling pathway, and enhanced the ratio of osteoprotegerin/receptor activator of nuclear factor kappa B ligand to maintain the balance of bone formation and resorption. Conclusions: Rosamultin attenuates acute HH-induced bone damage and improves abnormal bone remodeling in rats by inhibition of sclerostin expression and activation of the Wnt/β-catenin signaling pathway.
Wang, Xing-Min, Hui Liu, Jian-Yu Li, Jin-Xia Wei, Xia Li, Yong-Liang Zhang, Ling-Zhi Li, and Xi-Zheng Zhang. Rosamultin attenuates acute hypobaric hypoxia-induced bone injuries by regulation of sclerostin and its downstream signals. High Alt Med Biol. 21:273-286, 2020. Background: Rosamultin, one of the compounds extracted from Potentilla anserina L., exhibited significant pharmacological activity against oxidative stress and hypoxic injury in our previous study. However, the effect of rosamultin on bone damage induced by acute hypobaric hypoxia (HH) has not been thoroughly studied. Methods: In this study, we first investigated the protective effect of rosamultin against bone damage in rats following acute exposure to simulated high-altitude hypoxia. Furthermore, we explored the detailed mechanism involved in the regulation of rat bone remodeling by rosamultin in an acute HH environment through analysis of sclerostin expression and the regulation of downstream signaling pathways. Results: Pretreatment with rosamultin significantly reduced HH-induced oxidative stress and inflammation, improved bone metabolic abnormalities, and alleviated the imbalance in bone remodeling in rats exposed to acute HH. Rosamultin markedly downregulated the expression of sclerostin, activated the Wnt/β-catenin signaling pathway, and enhanced the ratio of osteoprotegerin/receptor activator of nuclear factor kappa B ligand to maintain the balance of bone formation and resorption. Conclusions: Rosamultin attenuates acute HH-induced bone damage and improves abnormal bone remodeling in rats by inhibition of sclerostin expression and activation of the Wnt/β-catenin signaling pathway.