Article
Biochemistry & Molecular Biology
Chao Liu, Yining Li, Ren Sheng, Xiaowan Han, Li Bao, Chenyin Wang, Weizhi Wang, Xinhai Jiang, Jiangxue Han, Lijuan Lei, Ni Li, Jing Zhang, Minghua Chen, Yan Li, Yexiang Wu, Shunwang Li, Yu Ren, Yanni Xu, Shuyi Si
Summary: The study demonstrated that the N-methylpyridine-chlorofuranformamide analog 3i1 shows promise in upregulating OPG activity, inhibiting RANKL-induced osteoclastogenesis, and promoting osteoblast differentiation, potentially serving as a new therapeutic agent for osteoporosis.
BIOORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Kanokkarn Phromnoi, Supachai Yodkeeree, Komsak Pintha, Sariya Mapoung, Maitree Suttajit, Chalermpong Saenjum, Pornngarm Dejkriengkraikul
Summary: This study investigated the effects of perilla leaf hexane fraction (PLH) in osteoporosis. The results showed that PLH can inhibit osteoclast differentiation and enhance osteoblast function.
Article
Pharmacology & Pharmacy
Guoju Hong, Lin Zhou, Guanqiang Zheng, Xiaoxia Zheng, Zhenqiu Chen, Wei He, Qiushi Wei
Summary: Liquiritin (LIQ) has the ability to inhibit osteoclast formation and bone-resorbing activity induced by RANKL, and it exerts its effects by reducing ROS levels and suppressing the Ca2+/MAPK-NFATc1 signaling pathway.
FRONTIERS IN PHARMACOLOGY
(2023)
Review
Pharmacology & Pharmacy
Jincai Chen, Xiaofei Liao, Juwen Gan
Summary: Osteoporosis is a disease characterized by continuous bone loss and increased fracture risk. Osthole, a natural compound derived from certain plants, shows promise in protecting against the development of osteoporosis and could potentially be developed into a treatment agent.
FRONTIERS IN PHARMACOLOGY
(2023)
Review
Pharmacology & Pharmacy
Shenglei Yang, Yuying Sun, Leonid Kapilevich, Xin'an Zhang, Yue Huang
Summary: Osteoporosis is a common skeletal disorder that primarily affects the elderly and postmenopausal women. Drug therapy is currently used as the main treatment, but long-term use can lead to drug resistance and side effects. Therefore, researchers are exploring natural plant compounds as an alternative. Curcumin, a natural phenolic compound, has shown potential as a candidate for treating osteoporosis due to its various pharmacological and biological activities. This review summarizes the mechanisms and therapeutic applications of curcumin in preventing and mitigating osteoporosis, providing valuable references for further research and development of curcumin.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Immunology
Jiachao Guo, Ranyue Ren, Zhou Guo, Kai Sun, Jinpeng He, Jingfan Shao, Xiaolin Wang
Summary: Osteoporosis is a systemic and endocrine bone disorder characterized by decreased bone mineral density, compromised bone strength, and destruction of trabecular structure. The excessive osteoclastogenesis and bone erosion contribute to the progression of the disease. However, existing medications have poor adherence and adverse reactions, highlighting the urgent need for novel therapies for osteoporosis.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Immunology
Hao Qu, Yuankang Zhang, Rongxin He, Nong Lin, Cong Wang
Summary: Postmenopausal osteoporosis is a chronic systemic metabolic disease caused by excessive bone resorption and reduced bone formation. Anethole, a natural compound, shows potential in inhibiting osteoclast differentiation, reducing bone resorption, and suppressing osteoclast-specific gene expression through blocking ERK and AKT signaling pathways. Our study suggests that anethole may have osteoprotective effects and be a potential treatment for osteoporosis.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Review
Chemistry, Medicinal
Sophia Ogechi Ekeuku, Kok-Lun Pang, Kok-Yong Chih
Summary: Caffeic acid, a metabolite of hydroxycinnamate and phenylpropanoid, acts as an antioxidant to reduce osteoclastogenesis and bone resorption. However, in some cases, it may have no effect on bone resorption or even impair bone mechanical properties in normal rats.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2021)
Article
Immunology
Cong Xu, Shu-Qing Jin, Chen Jin, Zi-Han Dai, Yu-Hao Wu, Gao-Lu He, Hai-Wei Ma, Chao-Yi Xu, Wen-Lai Fang
Summary: The study aimed to investigate the effect and mechanism of Cedrol (Ced) in estrogen-deficient osteoporosis. The results demonstrated that Ced mitigated RANKL-induced osteoclastogenesis by reducing ROS content and inhibiting NFATc1, NF-KB, and MAPK signaling pathways. Additionally, Ced-mediated anti-osteolytic property was observed in ovariectomized mice. Thus, this study revealed the anti-osteoporotic potential of Cedrol in Ginger and provided more pharmacological evidence for Ginger as a food or medicine for bone metabolic disease.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Cell Biology
Zhihai Cao, Yuan Xue, Jiaqian Wang
Summary: Osteoporosis is caused by decreased bone formation and increased bone absorption, with ferroptosis playing a key role. Ferroptosis may inhibit bone formation and promote bone absorption through oxidative stress, leading to osteoporosis.
Review
Endocrinology & Metabolism
Chenyu Zhu, Shiwei Shen, Shihua Zhang, Mei Huang, Lan Zhang, Xi Chen
Summary: Bone homeostasis is regulated by autophagy, which plays a critical role in the differentiation, apoptosis, and survival of bone cells. Oxidative stress induces autophagy as a protective response against cell damage. Understanding how autophagy regulates bone formation and bone resorption provides insights for potential therapeutic targets in osteoporosis.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Chemistry, Medicinal
Shuan-Jing Wang, Jiahui Zhang, Jing-Zan Zhang, Ruo-Nan Ning, Chen-Chen Li, Xing Xu, Min Jiang, Wen-Wei Qiu
Summary: A series of heterocyclic ring-fused derivatives of 20(S)-protopanaxadiol (PPD) were synthesized and evaluated for their inhibitory effects on RANKL-induced osteoclastogenesis. Compound 33 (SH491) showed the highest potency with 100% inhibition at 0.1 μM and 44.4% inhibition at 0.01 μM, surpassing the lead compound PPD. Cytotoxicity tests indicated that the inhibitory effect was not due to cytotoxicity, and SH491 also affected osteoblastogenesis.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Kangtao Jin, Lin Zheng, Lin Ye, Ziang Xie, Jiawei Gao, Chao Lou, Wenzheng Pan, Bin Pan, Shijie Liu, Zhenzhong Chen, Dengwei He
Summary: The study demonstrates that CSB6B suppresses osteoclast differentiation and bone resorption while enhancing osteoblast mineralization by inhibiting the NF-KB pathway and promoting Runx expression. In murine models, CSB6B has shown protective effects against pathological bone destruction and bone loss induced by estrogen deficiency. MIF inhibition by CSB6B could be a potential therapeutic approach for osteolytic bone disorders and osteoporosis.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Honglei Kang, Qian Guo, Yimin Dong, Renpeng Peng, Kehan Song, Jia Wang, Haiyang Liu, Meipeng Zhu, Hongjian Zhao, Hanfeng Guan, Feng Li
Summary: MAT2A is crucial for osteoclastogenesis and may be a potential therapeutic target for the treatment of osteoporosis.
Article
Oncology
Guoju Hong, Zhenqiu Chen, Xiaorui Han, Lin Zhou, Fengxiang Pang, Rishana Wu, Yingshan Shen, Xiaoming He, Zhinan Hong, Ziqi Li, Wei He, Qiushi Wei
Summary: The study revealed that Robinin could prevent bone resorption by inhibiting osteoclastogenesis mediated by RANKL, reducing ROS production, and regulating molecular signaling pathways, making it a potential drug for treating osteoporosis.
CLINICAL AND TRANSLATIONAL MEDICINE
(2021)
Article
Endocrinology & Metabolism
Aliya A. Khan, Lars Rejnmark, Mishaela Rubin, Peter Schwarz, Tamara Vokes, Bart Clarke, Intekhab Ahmed, Lorenz Hofbauer, Claudio Marcocci, Uberto Pagotto, Andrea Palermo, Erik Eriksen, Meryl Brod, Denka Markova, Alden Smith, Susanne Pihl, Sanchita Mourya, David B. Karpf, Aimee D. Shu
Summary: This study investigated the safety, tolerability, and efficacy of TransCon PTH in adults with hypoparathyroidism. The results showed that TransCon PTH enabled most participants to achieve independence from standard of care and improved their health-related quality of life.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Article
Endocrinology & Metabolism
Aliya A. Khan, Mishaela R. Rubin, Peter Schwarz, Tamara Vokes, Dolores M. Shoback, Claudia Gagnon, Andrea Palermo, Claudio Marcocci, Bart L. Clarke, Lisa G. Abbott, Lorenz C. Hofbauer, Lynn Kohlmeier, Susanne Pihl, Xuebei An, Walter Frank Eng, Alden R. Smith, Jenny Ukena, Christopher T. Sibley, Aimee D. Shu, Lars Rejnmark
Summary: TransCon PTH demonstrated efficacy in maintaining normocalcemia and allowing independence from conventional therapy in individuals with hypoparathyroidism. The treatment also showed significant improvements in health-related quality of life and hypoparathyroidism-related symptoms.
JOURNAL OF BONE AND MINERAL RESEARCH
(2023)
Article
Cardiac & Cardiovascular Systems
Farwah Iqbal, Florian Schlotter, Dakota Becker-Greene, Adrien Lupieri, Claudia Goettsch, Joshua D. Hutcheson, Maximillian A. Rogers, Shinsuke Itoh, Arda Halu, Lang Ho Lee, Mark C. Blaser, Andrew K. Mlynarchik, Sumihiko Hagita, Shiori Kuraoka, Hao Yu Chen, James C. Engert, Livia S. A. Passos, Prabhash K. Jha, Eric A. Osborn, Farouc A. Jaffer, Simon C. Body, Simon C. Robson, George Thanassoulis, Masanori Aikawa, Sasha A. Singh, Abhijeet R. Sonawane, Elena Aikawa
Summary: This study identified SORT1 as a key player in the pathophysiology of calcific aortic valve disease (CAVD) and explored its role in the transformation of valvular interstitial cells (VICs) into pathological phenotypes. It was found that SORT1 promotes CAVD through mediating valvular fibrosis and calcification. This study provides insight into the role of SORT1 in valve calcification and suggests that it could be a potential therapeutic target to inhibit the emergence of pathological phenotypes underlying CAVD.
EUROPEAN HEART JOURNAL
(2023)
Review
Biochemistry & Molecular Biology
Jonas Heyn, Marina Augusto Heuschkel, Claudia Goettsch
Summary: Mitochondria play crucial roles in regulating metabolism, cell death, and energy production. The maintenance of mitochondrial health is essential for cellular homeostasis. Recent studies have identified a novel cellular response called mitochondrial-derived vesicles (MDVs), which are released from mitochondria and can be degraded within lysosomes or peroxisomes. MDVs are implicated in cardiovascular disease (CVD) and may contribute to mitochondrial dysfunction. Furthermore, extracellular vesicles (EVs) have been found to contain mitochondrial content. This article provides an overview of MDV formation and trafficking, discusses the connection between MDVs and EV biogenesis, and explores their roles in CVD, as well as the potential cardioprotective effects of vesicle-mediated mitochondrial transfer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Endocrinology & Metabolism
Eva Maria Woelfel, Franziska Lademann, Haniyeh Hemmatian, Stephane Blouin, Phaedra Messmer, Lorenz C. Hofbauer, Bjoern Busse, Martina Rauner, Katharina Jaehn-Rickert, Elena Tsourdi
Summary: Hyperthyroidism causes secondary osteoporosis by promoting bone resorption. Osteocytic osteolysis and elevated tartrate-resistant acid phosphatase (TRAP) activity were observed in hyperthyroid mice. The bone microarchitecture and turnover recovered after treatment, but the osteocytic osteolysis effects were not reversed.
JOURNAL OF BONE AND MINERAL RESEARCH
(2023)
Article
Engineering, Biomedical
Sofie Dragoun Kolibova, Eva Maria Woelfel, Haniyeh Hemmatian, Petar Milovanovic, Herbert Mushumba, Birgit Wulff, Maximilian Neidhardt, Klaus Pueschel, Antonio Virgilio Failla, Annegreet Vlug, Alexander Schlaefer, Benjamin Ondruschka, Michael Amling, Lorenz C. Hofbauer, Martina Rauner, Bjoern Busse, Katharina Jaehn-Rickert
Summary: Type 1 diabetes mellitus (T1DM) is associated with increased bone fragility. Our study found accelerated osteocyte apoptosis and local mineralization in T1DM patients, suggesting that T1DM speeds up bone aging and impairs its biomechanical competence. Dysfunction of the osteocyte network hampers bone remodeling and repair, contributing to the increased fracture risk in T1DM individuals.
ACTA BIOMATERIALIA
(2023)
Article
Endocrinology & Metabolism
Manuel Gado, Annett Heinrich, Denise Wiedersich, Katrin Sameith, Andreas Dahl, Vasileia I. Alexaki, Michael M. Swarbrick, Ulrike Baschant, Ingo Grafe, Nikolaos Perakakis, Stefan R. Bornstein, Martina Rauner, Lorenz C. Hofbauer, Holger Henneicke
Summary: This study demonstrates that activation of the sympathetic nervous system through cold exposure or selective I33-adrenergic receptor agonist can alleviate the adverse metabolic effects caused by chronic glucocorticoid exposure. Cold exposure preserves the function of brown adipose tissue and reverses white adipose tissue lipid accumulation, correcting obesity, hyperinsulinemia, and hyperglycemia caused by glucocorticoids.
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
(2023)
Article
Engineering, Biomedical
Gloria Ruiz-Gomez, Juliane Salbach-Hirsch, Jan-Niklas Duerig, Linda Koehler, Kanagasabai Balamurugan, Sandra Rother, Sophie-Luise Heidig, Stephanie Moeller, Matthias Schnabelrauch, Giulia Furesi, Sophie Paehlig, Pedro M. Guillem-Gloria, Christine Hofbauer, Vera Hintze, M. Teresa Pisabarro, Joerg Rademann, Lorenz C. Hofbauer
Summary: The WNT signaling pathway is important for bone development and regeneration, and abnormalities in WNT ligands and inhibitors are associated with various bone diseases. This study focused on glycosaminoglycan (GAG) recognition by DKK1, a WNT inhibitor, and aimed to develop WNT signaling regulators. Through a multidisciplinary approach, researchers designed and synthesized GAG derivatives with improved neutralizing properties for DKK1. These derivatives showed increased WNT pathway activity and improved bone regeneration in experimental models. The findings suggest that rationally engineered GAG variants could be used as novel therapeutic approaches.
Article
Cardiac & Cardiovascular Systems
Joshua D. D. Hutcheson, Claudia Goettsch
Summary: Patients with CKD have a significantly increased risk of cardiovascular disease, primarily due to premature aging of blood vessels and heart and accelerated ectopic calcification. The presence of cardiovascular calcification is associated with higher risk in CKD patients. Disturbances in mineral homeostasis and comorbidities contribute to systemic cardiovascular calcification with various clinical consequences. This review discusses the heterogeneity in calcification patterns, the impact of mineral on tissue function, and potential therapeutic approaches to disrupt mineral nucleation and growth in CKD patients.
CIRCULATION RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Maria G. Ledesma-Colunga, Ulrike Baschant, Heike Weidner, Tiago C. Alves, Peter Mirtschink, Lorenz C. Hofbauer, Martina Rauner
Summary: In this study, the authors investigated the role of transferrin receptor 2 (Tfr2) in the pathogenesis of inflammatory arthritis. They found that Tfr2-deficient mice developed more severe joint inflammation and bone erosion compared to control mice. Further experiments suggested that Tfr2 deficiency promoted macrophage polarization towards a pro-inflammatory state, contributing to the progression of arthritis.
Article
Hematology
Julian Kamhieh-Milz, Lei Chen, Claudia Goettsch, Anna Maria Pfefferkorn, Anja Hofmann, Coy Brunssen, Gregor M. Mueller, Thomas Walther, Muhammad Imtiaz Ashraf, Guido Moll, Henning Morawietz, Janusz Witowski, Rusan Catar
Summary: This study analyzed the mechanism by which NOX2 contributes to Ang II-induced ET-1 production in human microvascular endothelial cells. The results showed that high-fat diet increased the expression of Ang II and ET-1 in wild-type mice, but not in Nox2-deficient mice. In vitro experiments revealed that Ang II promoted NOX2 expression through induction of the Oct-1 protein and increased production of superoxide anions. Inhibition of Oct-1 and superoxide attenuated Ang II-induced ET-1 production.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2023)
Article
Endocrinology & Metabolism
Souad Daamouch, Sylvia Thiele, Lorenz Hofbauer, Martina Rauner
Summary: The link between obesity and low bone strength is a significant medical concern. Previous research has shown that Dkk1, a Wnt inhibitor, is upregulated in bone tissue in obesity and drives obesity-induced bone loss. This study investigated the role of adipogenic Dkk1 in bone homeostasis and obesity-induced bone loss in mice. The results suggest that adipogenic Dkk1 plays a transient role in bone mass regulation during adolescence, but does not contribute to bone homeostasis or obesity-induced bone loss later in life.
ENDOCRINE CONNECTIONS
(2023)
Article
Medicine, General & Internal
Athanasios D. Anastasilakis, Stergios A. Polyzos, Panagiotis A. Vorkas, Athina Gkiomisi, Maria P. Yavropoulou, Martina Rauner, Panagiotis Nikolakopoulos, Stergios Papachatzopoulos, Polyzois Makras, Spyridon Gerou, Lorenz C. Hofbauer, Andrea Palermo, Elena Tsourdi
Summary: Menstrual cessation affects lipid metabolism. This study evaluated the effects of goserelin-induced menstrual cessation and subsequent menstrual restoration on lipid metabolism. The results showed that levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and apolipoprotein A1 increased during menstrual cessation, but remained unchanged during menstrual restoration.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Endocrinology & Metabolism
Mahdi Jaber, Lorenz C. Hofbauer, Christine Hofbauer, Georg N. Duda, Sara Checa
Summary: Bone regeneration is impaired in type 2 diabetes mellitus (T2DM), with alterations in MSC proliferation, migration, and osteoblast differentiation playing a significant role. Mechanical changes have minimal impact on reduced bone regeneration in T2DM. These findings have clinical implications for the treatment of bone fractures in patients with T2DM.
Article
Medicine, Research & Experimental
Lorenz C. Hofbauer, Franziska Lademann, Martina Rauner
Summary: Osteocytes, senescent cells implicated in bone loss disorders, have been shown to be effectively cleared through systemic senolysis, preventing age-related bone loss and mitigating bone marrow adiposity. Cell-specific senolysis in osteocytes alone had only a partial effect. Surprisingly, transplantation of senescent fibroblasts into young mice led to osteocyte senescence and bone loss. These findings on osteocyte senescence and the effects of remote senolysis suggest potential strategies against multisystem aging.
JOURNAL OF CLINICAL INVESTIGATION
(2023)