Olivier Duverger, Valentina Baena, Zulfeqhar A Syed, Janice S Lee
{"title":"Impaired Remodeling of Tight Junctions Associated with Loss of Enamel Rod Decussation in Tgfbr2<sup>G357W/+</sup> Mice.","authors":"Olivier Duverger, Valentina Baena, Zulfeqhar A Syed, Janice S Lee","doi":"10.1007/s00223-026-01541-7","DOIUrl":"10.1007/s00223-026-01541-7","url":null,"abstract":"<p><p>During enamel secretion, ameloblasts follow a complex coordinated movement that results in the enamel rods being arranged in a crisscross pattern that contributes significantly to its exceptional mechanical properties. We previously determined that mutations in the gene encoding TGF-β receptor 2 (TGFR-2) in humans (TGFBR2) and mice (Tgfbr2) result in the formation of fully mineralized enamel that exhibits impaired decussation of enamel rods. Using Tgfbr2<sup>G357W/+</sup> mice, we demonstrated that this phenotype was due to disrupted coordinated movement of ameloblasts during enamel secretion. In this study, we used focused ion beam scanning electron microscopy (FIB-SEM) to look more closely at the area of the apical terminal web (ATW) where the cells are connected via tight junctions. We show that ameloblasts from wild-type littermates exhibit an abrupt shift in orientation at the ATW while Tgfbr2<sup>G357W/+</sup> mice show no signs of such shift. Moreover, ZO-1 distribution at the ATW was abnormal in Tgfbr2<sup>G357W/+</sup> mice with reduced accumulation at the ATW and presence of clusters of the protein at the basal side. These results suggest that abrupt orientation shift at the ATW via dynamic remodeling of tight junctions is essential for rows of ameloblasts to deposit enamel rods in opposite directions.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"117 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13132921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brent Vasquez, Ai Thu Bui, Henry C Margolis, Elia Beniash
{"title":"Amelogenin Phosphorylation Affects Protein-Protein Interactions In Vivo.","authors":"Brent Vasquez, Ai Thu Bui, Henry C Margolis, Elia Beniash","doi":"10.1007/s00223-026-01530-w","DOIUrl":"https://doi.org/10.1007/s00223-026-01530-w","url":null,"abstract":"","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"117 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tong Yu, Andy Kin On Wong, Nina Z Heilmann, Kerri S Freeland, Bradley C Nindl, Kristen J Koltun, Andrew J Burghardt, Julie M Hughes, Peggy M Cawthon, Jane A Cauley, Elsa S Strotmeyer, Nancy E Lane
{"title":"Sex-Specific Associations of Radiographic Knee Osteoarthritis and Pain with Distal Tibia Bone Microarchitecture: the Study of Muscle, Mobility and Aging (SOMMA).","authors":"Tong Yu, Andy Kin On Wong, Nina Z Heilmann, Kerri S Freeland, Bradley C Nindl, Kristen J Koltun, Andrew J Burghardt, Julie M Hughes, Peggy M Cawthon, Jane A Cauley, Elsa S Strotmeyer, Nancy E Lane","doi":"10.1007/s00223-026-01531-9","DOIUrl":"https://doi.org/10.1007/s00223-026-01531-9","url":null,"abstract":"","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"117 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13111493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Guilherme H Souza Bomfim, Anna Zou, Fabio A Echeverry, Ai Thu Bui, Edisa de Oliveira Sousa, Bruno Luis Graciliano Silva, Lukasz Witek, William A Coetzee, Rodrigo S Lacruz
{"title":"Mechanosensitive Piezo1 Channels in Enamel Cells.","authors":"Guilherme H Souza Bomfim, Anna Zou, Fabio A Echeverry, Ai Thu Bui, Edisa de Oliveira Sousa, Bruno Luis Graciliano Silva, Lukasz Witek, William A Coetzee, Rodrigo S Lacruz","doi":"10.1007/s00223-026-01534-6","DOIUrl":"https://doi.org/10.1007/s00223-026-01534-6","url":null,"abstract":"<p><p>Ameloblasts are specialized epithelial cells that form enamel during the secretory and maturation stages, the latter involving an increase in Ca<sup>2+</sup> transport to mineralize the enamel crystals. During enamel formation, ameloblasts travel several microns while secreting a matrix and are surrounded by several cell layers in the confined space of the enamel organ. Presumably, ameloblasts are subjected to mechanical stimuli e.g. pressure, stretch. Mechanosensitive (MS) or stretch-gated channels are expressed in the membranes of many cells including mineralizing cells. The opening of MS channels occurs in response to physical stimuli and results in the influx of ions. Piezo1 is a non-selective class of MS channel permeable to Ca<sup>2+</sup> and hence it may contribute to Ca<sup>2+</sup> homeostasis in ameloblasts. Here we show that secretory and maturation stage ameloblasts express similar protein levels of Piezo1. Cultured rat primary secretory and maturation stage ameloblasts showed stretch-activated currents by patch-clamp. Ameloblasts loaded with the cytosolic Ca<sup>2+</sup> indicator Fura-2 were also stimulated with the Piezo1-selective activator Yoda1. We show that ameloblasts are sensitive to Piezo1 stimulation which evoked an increase in cytosolic Ca<sup>2+</sup>. This effect was inhibited by Piezo1 blockers. Mechanical analysis of the incisors of Piezo1 cKO mice showed no alterations in hardness or elastic modulus relative to littermate control mice. Our work provides the first evidence that Piezo1 channels are functional in both ameloblast stages and their activation leads to an elevation in cytosolic Ca<sup>2+</sup>, however, Piezo1 does not appear to be essential for enamel mineralization.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"117 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Clarifying the Distinction Between Pregnancy- and Lactation-Associated Osteoporosis and Transient Osteoporosis of the Hip.","authors":"Şansın Tüzün","doi":"10.1007/s00223-026-01533-7","DOIUrl":"https://doi.org/10.1007/s00223-026-01533-7","url":null,"abstract":"","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"117 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Iya Ghassib, Anusha Inti, Nushaba Hossain, Thomas Kim, Danielle Moon, Lu Han, Rawan Mohsen, Honghao Zhang, Nicholas Auyeung, Yuji Mishina, Daniela Mendonça, Darnell Kaigler, Teresita Bellido, Fei Liu
{"title":"Region- and Compartment-Specific Elevation of Bone Mass in Mice Following Tsc1 Deletion in 8-kb Dmp1-Cre-Expressing Cells.","authors":"Iya Ghassib, Anusha Inti, Nushaba Hossain, Thomas Kim, Danielle Moon, Lu Han, Rawan Mohsen, Honghao Zhang, Nicholas Auyeung, Yuji Mishina, Daniela Mendonça, Darnell Kaigler, Teresita Bellido, Fei Liu","doi":"10.1007/s00223-026-01532-8","DOIUrl":"https://doi.org/10.1007/s00223-026-01532-8","url":null,"abstract":"","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"117 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13111507/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dinne Nedjar, Arnaud Vanden Bossche, Christie Mitri, The Nghia Nguyen, Florian Hermans, Coralie Torrens, Nicolas Roubier, Elsa Vennat, David Montero, Lotfi Slimani, Hubert Marotte, Catherine Chaussain, Olivier Tabary, Françoise Tilotta
{"title":"Ano1 Antisense Therapy Improves Enamel Properties in Molars but not Amelogenesis in a Murine Model of Cystic Fibrosis.","authors":"Dinne Nedjar, Arnaud Vanden Bossche, Christie Mitri, The Nghia Nguyen, Florian Hermans, Coralie Torrens, Nicolas Roubier, Elsa Vennat, David Montero, Lotfi Slimani, Hubert Marotte, Catherine Chaussain, Olivier Tabary, Françoise Tilotta","doi":"10.1007/s00223-026-01500-2","DOIUrl":"https://doi.org/10.1007/s00223-026-01500-2","url":null,"abstract":"<p><p>Cystic fibrosis (CF) is a life-shortening inherited disorder caused by mutations in the gene encoding the Cystic Fibrosis Transmembrane conductance Regulator (CFTR), a protein that controls the transport of chloride ions across cell membranes. Defects in CFTR cause thick mucus, leading to chronic infections and inflammation in multiple organs. Severe mutations, such as G542X, that completely abolish the function of CFTR present major therapeutic challenges. One potential approach is to stimulate an alternative chloride channel, ANO1, which is repressed in patients by the small regulatory molecule microRNA-9. We recently showed that an antisense oligonucleotide (ASO) designed to restore ANO1 activity (Ano1 ASO) improved respiratory and digestive functions in a CF mouse model carrying the pathogenic G542X variant. As patients with severe forms of CF often display enamel defects, we aimed to investigate the impact of Ano1 ASO on enamel of G542X CF mice. Combining multiproxy imaging approaches, our data showed that Ano1 ASO initiated at postnatal day 8 partially rescued the enamel properties in molars, which have mainly formed before the onset of treatment. However, it did not correct enamel maturation in the continuously growing incisor. In contrast to CFTR, there was no significant increase in ANO1 expression in maturation-stage ameloblasts compared to secretion ameloblasts. These findings suggest that while stimulating ANO1 cannot compensate for the absence of CFTR during enamel maturation, it enhances the mechanical properties of the erupted teeth, likely by improving salivary properties. This work identifies a potential avenue for mitigating dental complications in patients with severe CF mutations.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"117 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}