Article
Cell Biology
Minhee Kim, Jingjing Lin, Jeong-Eun Huh, Jin Hee Park, Miyeon Go, Hana Lee, Donghyun Hwang, Han Sung Kim, Taesoo Kim, Daekee Lee, Soo Young Lee
Summary: The study revealed that TSPAN7 plays a crucial role in regulating the bone-resorbing function of osteoclasts by modulating actin ring formation. Deletion of Tm4sf2 led to significant defects in integrin-mediated actin ring formation, resulting in decreased bone resorption. The findings suggest that TSPAN7 acts as a novel modulator in osteoclasts.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Article
Multidisciplinary Sciences
Dan-yang Guo, Zhong-hua Chen, Yi-fei Fu, Yue-yue Li, Meng-nan Chen, Jun-jie Wu, Zheng-dong Yuan, Jun-Xing Ye, Xia Li, Feng-lai Yuan
Summary: By blocking the signaling pathway of integrin alpha(v)beta(3), cilengitide effectively inhibits the functionality and formation of osteoclasts, resulting in diminished adhesion and bone resorption. The expression of key signaling molecules associated with the osteoclast cytoskeleton are downregulated by cilengitide.
Article
Biochemistry & Molecular Biology
David Castro-Vazquez, Amalia Lamana, Paula Arribas-Castano, Irene Gutierrez-Canas, Raul Villanueva-Romero, Selene Perez-Garcia, Carmen Martinez, Yasmina Juarranz, Sara Fernandez de Cordoba, Isidoro Gonzalez-alvaro, Rosa P. Gomariz, Mar Carrion
Summary: The study found that VIP has an inhibitory effect on osteoclast differentiation and resorption activity in humans, mainly through negative regulation of NFATc1, demonstrating its bone-protective effects. Elevated serum VIP levels in early arthritis patients were associated with lower BMD loss and higher serum OPG concentration.
Article
Engineering, Biomedical
Xiaogang Wang, Luli Ji, Jing Wang, Changsheng Liu
Summary: Osteoclasts play a crucial role in bone homeostasis, and their dysregulation is associated with bone diseases. Current clinical strategies for managing osteoclasts often perturb bone metabolism. This study proposed a novel approach of regulating osteoclast differentiation through mechanical stimulation. The researchers created a hydrogel that mimicked the physiological bone microenvironment and found that matrix stiffness could direct osteoclast fate in vitro and in vivo. Selecting the optimum matrix stiffness could finely regulate osteoclast differentiation and potentially be used in bone tissue engineering strategies.
BIOACTIVE MATERIALS
(2023)
Review
Cell Biology
Driti Ashok, Laura Polcik, Svenja Dannewitz Prosseda, Tanja Nicole Hartmann
Summary: The bone marrow microenvironment plays a crucial role in the function and malignant transformation of hematopoietic stem cells. It is composed of various cell types, soluble factors, and extracellular matrix. The positioning of cells within this microenvironment depends on adhesion molecules and chemotactic signaling. The interaction between cell adhesion and metabolic pathways is essential for maintaining the stability of the bone marrow niche.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Cell Biology
Xinyue Liang, Yafei Hou, Lijuan Han, Shuxiang Yu, Yunyun Zhang, Xiumei Cao, Jianshe Yan
Summary: Bone homeostasis is maintained by a balance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption. ELMO1, as a regulator of Rac1, plays a crucial role in osteoclast differentiation and bone resorption, with Elmo1(-/-) mice exhibiting defective bone resorption and alleviated bone erosion in a rheumatoid arthritis model.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Huimin Hu, Xiaodong Wang, Yansheng Huang, Baorong He, Jinwen Zhu, Kai Sun, Chaoyang Deng, Yunshan Guo, Dingjun Hao, Bin Jian
Summary: The natural compound obacunone found in citrus fruits can inhibit osteoclast differentiation through modulating the Integrin-FAK-Src pathway, suggesting its potential as a therapeutic candidate for the treatment and prevention of bone diseases such as osteoporosis.
Article
Biochemistry & Molecular Biology
Parichart Toejing, Nithidol Sakunrangsit, Pinyada Pho-on, Chinnatam Phetkong, Asada Leelahavanichkul, Somyoth Sridurongrit, Matthew B. Greenblatt, Sutada Lotinun
Summary: In this study, transgenic mice expressing constitutively active TGF-beta receptor type I were found to have osteopenia due to increased osteoclast number and decreased osteoblast number, possibly by suppressing Hedgehog signaling pathways.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Pedro P. C. de Souza, Petra Henning, Ulf H. Lerner
Summary: Oncostatin M (OSM) is a potent stimulator of osteoclast formation and plays a significant role in bone remodeling by inducing RANKL in osteoblasts. Gene deletion of Osmr in mice leads to decreased osteoclast numbers and increased trabecular bone thickness. OSM can promote osteoblast differentiation and mineralization, but in vivo administration in adult animals does not significantly increase osteoclast formation due to the negative feedback loop through the osteoclastogenesis inhibitor WNT16.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Eun-Young Kim, Ji-Eun Kim, Young-Eun Kim, Bongkun Choi, Dong Hyun Sohn, Si-On Park, Yeon-Ho Chung, Yongsub Kim, William H. Robinson, Yong-Gil Kim, Eun-Ju Chang
Summary: The study found that parkin dysfunction associated with the progression of parkinsonism contributes to low bone mineral density. The decreased parkin in monocytes is linked to increased bone-resorbing activity of osteoclasts. Parkin-deficient mice exhibit an osteoporotic phenotype with increased bone-resorbing capacity and susceptibility to inflammatory arthritis.
CELL AND BIOSCIENCE
(2023)
Review
Biochemistry & Molecular Biology
Chun Feng, Zhaowei Xu, Xiaojie Tang, Haifei Cao, Guilong Zhang, Jiangwei Tan
Summary: This review summarizes the regulatory effect of the orphan nuclear receptor estrogen-related receptor (ERRα) on bone homeostasis and bone metastasis. The defined function of ERRα in bone is currently inconsistent and controversial, but it has the potential to become a target for clinical therapy.
Article
Biochemistry & Molecular Biology
Milene N. O. Moritz, Alyssa R. Merkel, Ean G. Feldman, Heloisa S. Selistre-de-Araujo, Julie A. Rhoades (Sterling)
Summary: The expression of α2β1 integrin is inversely correlated with bone metastatic potential in breast cancer. Overexpression of the α2 integrin subunit increases primary tumor growth and dissemination to bone, with no impact on tumor establishment and bone destruction.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Guangyu Sun, Emilie Guillon, Scott A. Holley
Summary: The study revealed that integrins exhibit different activation states in vivo, with integrins showing robust cell surface expression not being activated in this context, while activatable integrins have lower cell surface expression and higher intra-heterodimer dissociation constant.
Article
Multidisciplinary Sciences
Jeffrey T. McNamara, Kelsey E. Huntington, Samantha Borys, Chathuraka T. Jayasuriya, Laurent Brossay
Summary: The study shows that in the absence of SHP-2, uncontrolled proliferation of the BCSP subset may lead to the development of wrist cartilage tumors. These cells have a history of CD4 expression and wrist location tropism, explaining why the wrist is the main site of tumor development.
SCIENTIFIC REPORTS
(2021)
Article
Immunology
Camila O. S. Souza, Jefferson Elias-Oliveira, Marcella R. R. Pastore, Caroline Fontanari, Vanessa F. F. Rodrigues, Vanderlei Rodriguez, Luiz G. G. Gardinassi, Lucia H. Faccioli
Summary: This study found that CD18(low) mice chronically infected with Schistosoma mansoni exhibited reduced monocytes and patrolling monocytes, as well as abnormal polarization and function of macrophages, which may impact the process of inflammation and tissue repair.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Cell Biology
Lucy Y. Tao, Katarzyna B. Lagosz-Cwik, Jolanda M. A. Hogervorst, Ton Schoenmaker, Aleksander M. Grabiec, Tim Forouzanfar, Fridus A. van der Weijden, Teun J. de Vries
Summary: Research suggests that metformin has beneficial effects on the periodontal status of periodontitis patients by inhibiting osteoclast formation and activity, potentially benefiting the bone as a whole.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Biotechnology & Applied Microbiology
Elisabeth M. W. Eekhoff, Ruben D. de Ruiter, Bernard J. Smilde, Ton Schoenmaker, Teun J. de Vries, Coen Netelenbos, Edward C. Hsiao, Christiaan Scott, Nobuhiko Haga, Zvi Grunwald, Carmen L. De Cunto, Maja di Rocco, Patricia L. R. Delai, Robert J. Diecidue, Vrisha Madhuri, Tae-Joon Cho, Rolf Morhart, Clive S. Friedman, Michael Zasloff, Gerard Pals, Jae-Hyuck Shim, Guangping Gao, Frederick Kaplan, Robert J. Pignolo, Dimitra Micha
Summary: Fibrodysplasia ossificans progressiva (FOP) is a rare and devastating genetic disease where soft connective tissue turns into heterotopic bone. Although the genetic defect is known, effective treatments have been hindered by the complexity of the disease. Gene therapy shows promise as a therapeutic option for FOP, but the role of the immune system and the primary causative cell remain unknown.
HUMAN GENE THERAPY
(2022)
Article
Rheumatology
Alejandro Rodriguez Ruiz, Marcella van Hoolwerff, Sara Sprangers, Eka Suchiman, Ton Schoenmaker, Petra Dibbets-Schneider, Johan L. Bloem, Rob G. H. H. Nelissen, Christian Freund, Christine Mummery, Vincent Everts, Teun J. de Vries, Yolande F. M. Ramos, Ingrid Meulenbelt
Summary: The study demonstrates the mechanism by which the readthrough mutation in TNFRSF11B leads to a bidirectional phenotype of subchondral bone turnover and cartilage mineralization in chondrocalcinosis patients. OPG-XL expression results in excessive fibrosis in cartilage and high mineralization in bone, accompanied by altered gene expression of MGP and DIO2.
Review
Medicine, General & Internal
Ton Schoenmaker, Amine Dahou Bouchankouk, Semih ozkan, Marjolijn Gilijamse, Elinor Bouvy-Berends, Coen Netelenbos, Frank Lobbezoo, Elisabeth Marelise W. Eekhoff, Teun J. de Vries
Summary: Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder characterized by abnormal bone formation in the muscles, tendons, and ligaments. This study aimed to evaluate the age of onset and location of bone formation and the resulting functional restrictions in the jaw of FOP patients. The results showed that bone formation is more common in females and trauma-induced bone formation occurs at a younger age than spontaneous bone formation. Additionally, the location of bone formation in the maxillofacial region affects the degree of restriction in jaw movement.
FRONTIERS IN MEDICINE
(2022)
Article
Dentistry, Oral Surgery & Medicine
Sune Demant, Ton Schoenmaker, Sophie M. G. van Erck, Sally Dabelsteen, Teun J. de Vries, Lars Bjorndal
Summary: The formation of dense connective tissue within the dental pulp and its association with pulpal inflammation in teeth with advanced carious lesions were investigated in this study. In addition, the study investigated whether inflammation affects the expression of markers related to chondrogenesis/osteogenesis in pulp cells in vitro.
INTERNATIONAL ENDODONTIC JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Ruben D. D. de Ruiter, Lisanne E. E. Wisse, Ton Schoenmaker, Maqsood Yaqub, Gonzalo Sanchez-Duffhues, E. Marelise W. Eekhoff, Dimitra Micha
Summary: FOP is an ultra-rare disease caused by genetic defects in the ACVR1 gene. We found that FOP patients have elevated Activin A production in their fibroblasts, and TGF beta 1 is a specific stimulant of Activin A in FOP. This study is the first to identify TGF beta 1 as a triggering factor of Activin A production in FOP, suggesting it as a possible therapeutic target.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Bernard J. Smilde, Esmee Botman, Teun J. de Vries, Ralph de Vries, Dimitra Micha, Ton Schoenmaker, Jeroen J. W. M. Janssen, Elisabeth M. W. Eekhoff
Summary: Fibroblasts play a crucial role in maintaining the extracellular matrix of connective tissues. Recent studies have found donor-derived fibroblasts in bone marrow transplant recipients, though some findings were not replicated. This systematic review provides an overview of hematopoietic stem cells differentiating into fibroblasts in various tissues, revealing evidence of fibroblasts derived from hematopoietic stem cells in almost all organs.
Article
Biochemistry & Molecular Biology
Ton Schoenmaker, Joy Zwaak, Bruno G. Loos, Richard Volckmann, Jan Koster, E. Marelise W. Eekhoff, Teun J. de Vries
Summary: Fibrodysplasia Ossificans Progressiva (FOP) is a rare genetic disease characterized by progressive heterotopic ossification that leads to immobility and premature death. It is caused by a mutation in the ACVR1 gene, resulting in altered response to Activin-A. Activin-A induces changes in osteoclastogenesis at the gene expression level, regardless of the presence of the mutated ACVR1 receptor. RNA sequencing analysis revealed differentially expressed genes and enriched pathways associated with osteoclast differentiation, cell fusion, and inflammation. These findings suggest that Activin-A plays a significant role in gene expression during osteoclast formation in FOP.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Karina E. Pigeaud, Melanie L. Rietveld, Aster F. Witvliet, Jolanda M. A. Hogervorst, Chen Zhang, Tim Forouzanfar, Nathalie Bravenboer, Ton Schoenmaker, Teun J. de Vries
Summary: Sclerostin is an inhibitor of bone formation produced by osteocytes, and it has been reported to be expressed in periodontal ligament fibroblasts as well. This study aimed to explore the role of sclerostin and its inhibitor romosozumab in osteogenesis and osteoclastogenesis. The results showed that sclerostin did not affect the osteogenic capacity of periodontal ligament fibroblasts, while romosozumab slightly reduced osteoclast formation in co-cultures with peripheral blood mononuclear cells at high concentrations. Further analysis revealed significant differences in the expression of SOST and its receptors between osteocytes and periodontal ligament cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Endocrinology & Metabolism
Teun J. de Vries, Antonella S. Kleemann, Jianfeng Jin, Ton Schoenmaker
Summary: Metformin has differential effects on bone cells, promoting bone formation while inhibiting bone resorption. It lowers the expression of negative regulators of bone formation in osteocytes and shifts the osteoblasts' regulation of bone resorption towards decrease RANKL expression and increase OPG expression. Metformin also activates bone formation parameters in osteoblast lineage cells and inhibits osteoclast formation and activity. These effects are likely mediated by the activation of phosphorylated AMP kinase (AMPK). Overall, metformin shows promising potential as a drug in the field of bone research.
CURRENT OSTEOPOROSIS REPORTS
(2023)