Article
Pharmacology & Pharmacy
Yongjie Chen, Linlin Zhang, Zongguang Li, Zuoxing Wu, Xixi Lin, Na Li, Rong Shen, Guojun Wei, Naichun Yu, Fengqing Gong, Gang Rui, Ren Xu, Guangrong Ji
Summary: Mogrol, an active component of Siraitia grosvenorii, exhibits anti-inflammatory, anticancer and neuroprotective effects. This study demonstrated that mogrol dose-dependently inhibited osteoclast formation and function by regulating gene expression and signaling pathway. Furthermore, mogrol reduced bone mass loss in postmenopausal mice, suggesting its promising potential for osteoporosis prevention or therapy.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Endocrinology & Metabolism
Mengbo Zhu, Wenbin Xu, Jiuzhou Jiang, Yining Wang, Yanjing Guo, Ruijia Yang, Yaqiong Chang, Bin Zhao, Zhenyu Wang, Jianfeng Zhang, Te Wang, Liqin Shangguan, Shaowei Wang
Summary: The study found that peiminine can inhibit the differentiation and function of OCs by regulating the levels of specific genes and proteins, with potential targets including NF-kappa B and ERK1/2 signaling pathways. In an animal model, peiminine can alleviate bone loss in ovariectomized mice.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Immunology
Rong Hu, Libo Chen, Xiaolong Chen, Zhong Xie, Chao Xia, Yong Chen
Summary: Aloperine has been shown to inhibit osteoclast activity and formation mediated by RANKL, indicating its potential as a new drug for the prevention and treatment of postmenopausal osteoporosis.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Meipeng Zhu, Qian Guo, Honglei Kang, Renpeng Peng, Yimin Dong, Yayun Zhang, Sibo Wang, Haiyang Liu, Hongjian Zhao, Zijian Dong, Kehan Song, Shimeng Xu, Pengju Wang, Liangxi Chen, Jian Liu, Feng Li
Summary: Fatty amide hydrolase (FAAH) is involved in various biological processes and may play an important role in osteoclastogenesis. Inhibition of FAAH in bone marrow-derived macrophages (BMMs) suppressed osteoclastogenesis and bone resorption. The FAAH inhibitor PF-04457845 improved bone loss in mice, and its effects were mediated through the NF-kappa B and MAPK pathways. Targeting FAAH may be a promising strategy for treating osteoclast-related diseases, particularly osteoporosis.
Article
Chemistry, Medicinal
Xuedong Li, Xixi Lin, Zuoxing Wu, Yuangang Su, Jiamin Liang, Runfeng Chen, Xue Yang, Lei Hou, Jinmin Zhao, Qian Liu, Feng Xu
Summary: The study demonstrates that PRI has therapeutic potential in treating osteolytic diseases like osteoporosis by inhibiting osteoclast formation and bone resorption activity both in vitro and in vivo. PRI exerts its effects through the suppression of NF-κB and ERK MAPK signaling pathways, preventing the production of mature osteoclasts.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2021)
Article
Biochemistry & Molecular Biology
Xin Liu, Xiaosa Xu, Jinping Li, Liying Shi, Ying Zeng, Siyuan Tang, Wei Liu, Lujuan Jia, Yuhong Li, Jie Zhang
Summary: In this study, it was discovered that isobavachalcone, derived from the traditional Chinese herb Psoralea corylifolia Linn, can inhibit osteoclastogenesis and bone resorption. The mechanism involves the suppression of NF-κB activation and downregulation of osteoclastic-specific genes and proteins. This suggests that isobavachalcone may have potential as a therapeutic compound for the treatment of osteoporosis and other metabolic bone diseases.
BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY
(2023)
Article
Nutrition & Dietetics
Junquan Tian, Xuetai Bao, Fan Yang, Xiongzhuo Tang, Qian Jiang, Yuying Li, Kang Yao, Yulong Yin
Summary: Age-related osteoporosis is a common disease in the elderly, mainly caused by excessive activity of osteoclasts. Most approved drugs inhibit osteoclasts to treat osteoporosis. This study shows that supplementing dimethyl alpha-ketoglutarate (DM-AKG) can inhibit the differentiation of osteoclasts. The mechanism involves regulating NF-kappa B signaling pathway and oxidative phosphorylation through PHD1-dependent manner.
Article
Multidisciplinary Sciences
Lijuan Jiang, Wenlin Qiu, Xuefei Hedrich, Xiaoru Duan, Xiaoxiao Han, Tong Yu, Shenghui Wen, Zhijun Luo, Ruizhi Feng, Yao Teng, Haifeng Yin, Christian M. Hedrich, Guo-Min Deng
Summary: The study found that glucocorticoids induce osteoporosis by inhibiting FcγRI and suppressing IgG-induced inflammation, while IgG effectively suppresses glucocorticoid-induced osteoporosis by inhibiting FcγRI. These findings may contribute to the development of therapeutic strategies for osteoporosis.
Article
Multidisciplinary Sciences
Mineon Park, Yong Jin Cho, Bora Kim, Young Jong Ko, Yuria Jang, Yeon Hee Moon, Hoon Hyun, Wonbong Lim
Summary: The study suggests that RANKL promotes migration and invasion of PCa cells through EMT, and inhibiting RANKL signaling may help prevent the metastasis of prostate cancer.
SCIENTIFIC REPORTS
(2021)
Review
Endocrinology & Metabolism
Yue Wu, Yunjiao Yang, Lan Wang, Yiding Chen, Xuke Han, Lisha Sun, Huizhen Chen, Qiu Chen
Summary: Osteoporosis is a bone disease characterized by low bone quality and density, causing bone fragility and vulnerability to fractures. Increased osteoclast differentiation and activity contribute to bone loss, a common manifestation of osteoporosis. The TNF-a/NF-κB inflammatory pathway plays a key role in regulating osteoclast formation, along with the classical RANKL/RANK/OPG pathway. Probiotics, particularly Bifidobacterium, have shown potential beneficial effects on bone health by modulating this pathway. This review discusses the molecular mechanisms of the TNF-a/NF-κB pathway in osteoclast formation and explores the secretions produced by Bifidobacterium, providing new directions for future research.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Cell Biology
Jin Ha Park, Jiae Lee, Gong-Rak Lee, Minjeong Kwon, Hye In Lee, Narae Kim, Hee Jin Kim, Mi-Ock Lee, Woojin Jeong
Summary: Cholesterol sulfate (CS) activates retinoic acid-related orphan receptor a (ROR alpha). CS and ROR alpha inhibit osteoclast differentiation. The mechanism involves the AMPK-Sirt1 axis, leading to NF-kappa B inhibition. CS also induces apoptosis and protects against bone loss in mouse models.
JOURNAL OF CELLULAR PHYSIOLOGY
(2023)
Article
Cell Biology
Xiaolong Yu, Jiawei Hu, Xinming Yang, Qiang Xu, Hangjun Chen, Ping Zhan, Bin Zhang
Summary: Sesamin has been found to inhibit osteoclast activation and bone resorption by blocking signaling pathways, making it a promising phytochemical agent for the treatment of osteolysis-related diseases caused by inflammation and excessive osteoclast activation.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2023)
Article
Medicine, Research & Experimental
Fan Yang, Yuangang Su, Jiamin Liang, Keyi Wang, Haoyu Lian, Junchun Chen, Jiake Xu, Jinmin Zhao, Qian Liu
Summary: Postmenopausal osteoporosis is a chronic metabolic disease characterized by low bone mineral density and bone fragility. In this study, it was found that Casticin inhibits osteoclast activation and differentiation induced by the receptor activator of nuclear factor-κB ligand. Casticin also prevents bone loss and reduces osteoclast activity in vivo, suggesting its potential as a preventive treatment for osteoporosis.
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
(2023)
Article
Medicine, Research & Experimental
Yu-Ting Cheng, Jian Liao, Qian Zhou, Hua Huo, Lucas Zellmer, Zheng-Long Tang, Hong Ma, Wei Hong, Dezhong Joshua Liao
Summary: Ovariectomy results in bone loss by increasing osteoblast apoptosis and inhibiting osteoclast apoptosis. Zoledronic acid exerts its therapeutic effects in the mandible by counteracting these cellular and molecular effects of ovariectomy.
EXPERIMENTAL BIOLOGY AND MEDICINE
(2021)
Article
Multidisciplinary Sciences
Yin Cheng, Haixia Liu, Jing Li, Yujie Ma, Changheng Song, Yuhan Wang, Pei Li, Yanjing Chen, Zhiguo Zhang
Summary: This study investigated the influence of different culture conditions on osteoclast differentiation in RAW264.7 cells. The results showed that RANKL treatment and cell density were important factors for osteoclast formation, while the addition of M-CSF had little effect. This research provides valuable insights into the optimal conditions for studying osteoclast function and mechanism.
Article
Medicine, Research & Experimental
Tianyu Xie, Wenyu Feng, Mingwei He, Xinli Zhan, Shijie Liao, Juliang He, Zhaojie Qin, Feicui Li, Jiake Xu, Yun Liu, Qingjun Wei
Summary: Osteosarcoma is a common malignant bone tumor in children and adolescents, and the five-year survival rate is estimated to be around 70%. This study found that high expression of EVI2B gene is associated with good prognosis in osteosarcoma patients.
EXPERIMENTAL BIOLOGY AND MEDICINE
(2023)
Article
Multidisciplinary Sciences
Jianbo He, Lin Zheng, Xiaojuan Li, Furong Huang, Sitao Hu, Lei Chen, Manya Jiang, Xianfeng Lin, Haibo Jiang, Yifan Zeng, Tianshen Ye, Dingkun Lin, Qian Liu, Jiake Xu, Kai Chen
Summary: This study aimed to explore the therapeutic potential of Obacunone (OB) on osteoporosis and its rudimentary mechanisms. In vitro and in vivo experiments showed that OB suppressed the formation and function of osteoclasts. Mechanistically, OB interacted with macrophage migration inhibitory factor (MIF), attenuating receptor activator of nuclear factor kappa B (NF-KB) ligand (RANKL)-induced signaling pathways. This led to a decrease in the expression level of the master transcriptional factor of osteoclastogenesis, nuclear factor of activated T cells 1 (NFATc1), and its downstream osteoclast-specific proteins. OB also alleviated estrogen deficiency-induced osteoporosis by targeting MIF and inhibiting hyperactive osteoclasts.
JOURNAL OF ADVANCED RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Weiguang Lu, Chao Zheng, Hongyang Zhang, Pengzhen Cheng, Sheng Miao, Huanbo Wang, Ting He, Jing Fan, Yaqian Hu, He Liu, Liyuan Jia, Xue Hao, Zhuojing Luo, Jiake Xu, Qiang Jie, Liu Yang
Summary: The imbalance of bone homeostasis leads to bone degenerative diseases, such as osteoporosis. The Hedgehog (Hh) signaling pathway plays a crucial role in limb and joint development, but its specific role in bone homeostasis is not well understood. This study discovered that the Hh signaling pathway is gradually enhanced during osteoclast differentiation, and its inactivation affects osteoclast formation and osteoclast-osteoblast coupling. The study also revealed the positive regulation of osteoclast differentiation by Hh signaling through the transactivation of Traf6 and stabilization of TRAF6 protein. In addition, connective tissue growth factor (CTGF) was identified as a bone formation-stimulating factor regulated by Hh signaling and its loss contributed to osteopenia. This research provides mechanistic and therapeutic insights into osteoporosis by highlighting the importance of Hh signaling in maintaining bone homeostasis.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Medicine, Research & Experimental
Fan Yang, Yuangang Su, Jiamin Liang, Keyi Wang, Haoyu Lian, Junchun Chen, Jiake Xu, Jinmin Zhao, Qian Liu
Summary: Postmenopausal osteoporosis is a chronic metabolic disease characterized by low bone mineral density and bone fragility. In this study, it was found that Casticin inhibits osteoclast activation and differentiation induced by the receptor activator of nuclear factor-κB ligand. Casticin also prevents bone loss and reduces osteoclast activity in vivo, suggesting its potential as a preventive treatment for osteoporosis.
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
(2023)
Article
Cell Biology
Shangfu Li, Dian Teguh, Depeng Wu, Lesong Liu, Chaofeng Hu, Jinbo Yuan, Charles A. Inderjeeth, Jiake Xu
Summary: This study investigated the effects of acetylcholinesterase inhibitors (AChEIs) on osteoclast differentiation and function. The findings showed that AChEIs, particularly Donepezil and Rivastigmine, can inhibit osteoclastogenesis and bone resorption by regulating MAPK and NFATc1 signaling pathways through downregulating AChE. These results have important clinical implications for elderly patients with dementia and osteoporosis.
JOURNAL OF CELLULAR PHYSIOLOGY
(2023)
Review
Cell Biology
Emel Rothzerg, Wendy N. Erber, Christopher L. M. H. Gibbons, David Wood, Jiake Xu
Summary: Osteohematology is an emerging field studying the interaction between hematopoietic and bone stromal cells to understand hematological and skeletal malignancies and diseases. The Notch signaling pathway plays critical roles in embryonic development and cancer progression, including osteosarcoma, leukemia, and multiple myeloma. Dysregulation of Notch-mediated malignant cells disrupts normal bone and bone marrow function, leading to disorders such as osteoporosis and bone marrow dysfunction. This mini-review summarizes the interplay between cells in bone and bone marrow under the Notch signaling pathway in both physiological and tumor microenvironments.
JOURNAL OF CELLULAR PHYSIOLOGY
(2023)
Article
Multidisciplinary Sciences
Pei Ying Ng, Amy B. P. Ribet, Qiang Guo, Benjamin H. Mullin, Jamie W. Y. Tan, Euphemie Landao-Bassonga, Sebastien Stephens, Kai Chen, Jinbo Yuan, Laila Abudulai, Maike Bollen, Edward T. T. T. Nguyen, Jasreen Kular, John M. Papadimitriou, Kent Soe, Rohan D. Teasdale, Jiake Xu, Robert G. Parton, Hiroshi Takayanagi, Nathan J. Pavlos
Summary: Using organelle-resolution proteomics, the authors identified Slc37a2 as a sugar transporter in osteoclast secretory lysosomes. They found that Slc37a2 is required for the maintenance of skeletal bone mass and that its deficiency leads to high bone mass in mice. This study provides new insights into the molecular composition and spatiotemporal organization of secretory lysosomes in osteoclasts.
NATURE COMMUNICATIONS
(2023)
Review
Pharmacology & Pharmacy
Sipin Zhu, Ping Sun, Samuel Bennett, Oscar Charlesworth, Renxiang Tan, Xing Peng, Qiang Gu, Omar Kujan, Jiake Xu
Summary: This review summarizes the recent research progress of Parthenolide (PTL) as a medicinal compound, including its therapeutic effects on skeletal diseases, cancers, and inflammation-induced cytokine storm. Mechanistic investigations reveal that PTL predominantly inhibits NF-kappa B activation and other signaling pathways. It is also proposed that PTL could inhibit cytokine storms triggered by COVID-19 via blocking the activation of NF-kappa B signaling. Understanding the pharmacologic properties of PTL will assist in developing its therapeutic application for medical conditions such as arthritis, osteolysis, periodontal disease, cancers, and COVID-19-related disease.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Genetics & Heredity
Sarah Rashid, Scott G. Wilson, Kun Zhu, John P. Walsh, Jiake Xu, Benjamin H. Mullin
Summary: This study analyzed the transcriptome of human peripheral blood mononuclear cells and their differentiated osteoclast-like cells in culture, identifying differentially expressed genes and associated biological pathways in the progression of osteoporosis. Several well-established osteoclast genes were significantly upregulated in osteoporosis, and the upregulated genes were involved in cell division, migration, adhesion, as well as oxidative phosphorylation, glycolysis, lysosome, and focal adhesion pathways.
Review
Cell Biology
Liwei Mao, Lian Wang, Jiake Xu, Jun Zou
Summary: Integrins play a crucial role in cell-extracellular matrix adhesion and cytokine receptor signal transduction, regulating bone metabolism. Recent studies have uncovered the involvement of integrins in bone metabolism pathways and their interaction with novel cytokines. Integrins act as transducers, mediating the effects of mechanical stress, fluid shear stress, microgravity, hypergravity, and other physical factors on bone-related cells. They also play a role in mediating bone metastasis of various cancers. Targeted therapy involving integrins shows promising potential for bone metabolic diseases. This review provides insights into the latest research on integrins in bone metabolism and metastasis and offers a vision for treatment strategies.
CELL DEATH DISCOVERY
(2023)
Article
Multidisciplinary Sciences
Minglian Xu, Dezhi Song, Xiaoxiao Xie, Yiwu Qin, Jian Huang, Chaofeng Wang, Junchun Chen, Yuangang Su, Jiake Xu, Jinmin Zhao, Qian Liu
Summary: This study found that CG inhibits osteoclast differentiation and function by inhibiting the activation of NFATc1 and ultimately osteoclast formation by inhibiting RANKL-mediated Ca2+ oscillation and the NF-KB/MAPK signaling pathway. CG also improved bone loss in ovariectomized mice, suggesting its potential for the prevention and treatment of osteoporosis.
Article
Multidisciplinary Sciences
Weilian Bao, Yan You, Jiahui Ni, Hui Hou, Jiaren Lyu, Guize Feng, Yirui Wang, Keyuan You, Sulin Zhang, Lijie Zhang, Xinyue Cao, Xu Wang, Haidong Li, Hong Li, Jiake Xu, Chenying Liu, Xiaomin Luo, Peng Du, Daofeng Chen, Xiaoyan Shen
Summary: Intestinal stem cells (ISCs) play a crucial role in the treatment of inflammatory bowel disease, and the availability of cholesterol is critical for their stemness. This study identifies sorting nexin 10 (SNX10) as essential for maintaining ISCs stemness by increasing intracellular cholesterol synthesis. The inhibition of SNX10 shows potential as a therapeutic strategy for patients with Crohn's disease.
Article
Oncology
Wenyu Feng, Haiyingjie Lin, Emel Rothzerg, Dezhi Song, Wenxiang Zhao, Tingting Ning, Qingjun Wei, Jinmin Zhao, David Wood, Yun Liu, Jiake Xu
Summary: Osteosarcoma (OS) is a common primary cancer in the skeletal system, with a high rate of lung metastasis, local recurrence, and death. The role of TRAIL receptors in OS has not been fully understood. This study used RNA-seq and scRNA-seq to investigate the expression profile of four TRAIL receptors in human OS cells. The results showed that TNFRSF10B and TNFRSF10D are differentially expressed in OS cells, while TNFRSF10A and TNFRSF10C remained stable. Furthermore, these receptors were most abundantly expressed in endothelial cells of OS tissues, providing a potential therapeutic target for OS and other cancers.
CANCER INFORMATICS
(2023)
Review
Cell & Tissue Engineering
Jialong Hou, Jian Liu, Zhixian Huang, Yining Wang, Hanbing Yao, Zhenxin Hu, Chengge Shi, Jiake Xu, Qingqing Wang
Summary: The composition and critical functions of membrane microdomains in osteoclasts need to be further characterized to understand their roles in bone diseases.
Article
Pharmacology & Pharmacy
Xiaoliang Feng, Zhijuan Liu, Yuangang Su, Haoyu Lian, Yijie Gao, Jinmin Zhao, Jiake Xu, Qian Liu, Fangming Song
Summary: In this study, TSG was found to inhibit OCs differentiation and bone resorption by reducing ROS production and mitochondrial function. Additionally, TSG increased ROS scavenging enzymes by inhibiting Nrf2 degradation and thereby reducing RANKL-induced oxidative stress.
BIOCHEMICAL PHARMACOLOGY
(2023)