Pristimerin Protects Against OVX-Mediated Bone Loss by Attenuating Osteoclast Formation and Activity via Inhibition of RANKL-Mediated Activation of NF-kappa B and ERK Signaling Pathways
Introduction: Osteoporosis is an osteolytic bone condition characterized by decreased bone strength and increased bone fragility. It is the result of elevated formation or activity of bone-resorbing osteoclasts. Although current therapeutic agents are efficacious against osteoclast-mediated bone loss, detrimental side effects preclude the long-term use of these agents. Pristimerin (PRI) is a naturally occurring quinone-methide triterpenoid that has been revealed to exert anti-inflammatory and anti-tumor effects via regulating various signaling cascades including NF-kappa B and MAPK activation. Methods: The bone marrow macrophages were used to confirm the anti-osteoclastic and anti-resorptive functions of PRI in vitro. An in vivo ovariectomy (OVX) model was applied to verify the function of PRI protecting bone loss. Results: PRI abolished the early activation of NF-kappa B and ERK MAPK signal cascades thereby thwarting the downstream expression of c-Fos and NFATc1, which prevented the production of mature osteoclasts. In vivo, PRI protects mice against ovariectomy (OVX)-mediated bone loss by diminishing osteoclast formation and bone resorptive activity. Conclusion: Our study shows that PRI demonstrates therapeutic potential in the effective treatment against osteoclast-induced osteolytic diseases like osteoporosis.
基金：
Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81770254, 81970236]; Natural Science Foundation of Guangxi ProvinceNational Natural Science Foundation of Guangxi Province [2018GXNSFAA050092]
第一作者机构：[1]Guangxi Med Univ, Guangxi Key Lab Regenerat Med, Nanning 530021, Guangxi, Peoples R China[2]Guangxi Med Univ, Guangxi Collaborat Innovat Ctr Biomed, Nanning 530021, Guangxi, Peoples R China
共同第一作者：
通讯作者：
通讯机构：[1]Guangxi Med Univ, Guangxi Key Lab Regenerat Med, Nanning 530021, Guangxi, Peoples R China[2]Guangxi Med Univ, Guangxi Collaborat Innovat Ctr Biomed, Nanning 530021, Guangxi, Peoples R China[5]Guangxi Med Univ, Affiliated Hosp 1, Orthopaed Dept, Res Ctr Regenerat Med, Nanning 530021, Guangxi, Peoples R China[6]Jiaotong Univ, Sch Med, Peoples Hosp Shanghai 9, Dept Subject Planning Shanghai, Shanghai 200011, Peoples R China[*1]Department of Subject Planning Shanghai, Ninth People’s Hospital Shanghai, Jiaotong University School of Medicine, Shanghai, People’s Republic of China[*2]Research Centre for Regenerative Medicine, Orthopaedic Department, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, People’s Republic of China
推荐引用方式(GB/T 7714)：
Li Xuedong,Lin Xixi,Wu Zuoxing,et al.Pristimerin Protects Against OVX-Mediated Bone Loss by Attenuating Osteoclast Formation and Activity via Inhibition of RANKL-Mediated Activation of NF-kappa B and ERK Signaling Pathways[J].DRUG DESIGN DEVELOPMENT AND THERAPY.2021,15:61-74.doi:10.2147/DDDT.S283694.
APA：
Li, Xuedong,Lin, Xixi,Wu, Zuoxing,Su, Yuangang,Liang, Jiamin...&Xu, Feng.(2021).Pristimerin Protects Against OVX-Mediated Bone Loss by Attenuating Osteoclast Formation and Activity via Inhibition of RANKL-Mediated Activation of NF-kappa B and ERK Signaling Pathways.DRUG DESIGN DEVELOPMENT AND THERAPY,15,
MLA：
Li, Xuedong,et al."Pristimerin Protects Against OVX-Mediated Bone Loss by Attenuating Osteoclast Formation and Activity via Inhibition of RANKL-Mediated Activation of NF-kappa B and ERK Signaling Pathways".DRUG DESIGN DEVELOPMENT AND THERAPY 15.(2021):61-74
