Jun Wang1, Alison M Muir2, Yinshi Ren3, Dawiyat Massoudi2, Daniel S Greenspan2, Jian Q Feng4. 1. Biomedical Sciences, Texas A&M College of Dentistry, Dallas, Texas; State Key Laboratory of Oral Diseases, Department of Periodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China. 2. Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin. 3. Biomedical Sciences, Texas A&M College of Dentistry, Dallas, Texas. 4. Biomedical Sciences, Texas A&M College of Dentistry, Dallas, Texas. Electronic address: JFeng@tamhsc.edu.
Abstract
INTRODUCTION: Mutations in the proteinase bone morphogenetic protein-1 (BMP1) were recently identified in patients with osteogenesis imperfecta, which can be associated with type 1 dentinogenesis imperfecta. BMP1 is co-expressed in various tissues and has overlapping activities with the closely related proteinase mammalian tolloid-like 1 (TLL1). In this study we investigated whether removing the overlapping activities of BMP1 and TLL1 affects the mineralization of tooth root dentin. METHODS: Floxed alleles of the BMP1 and TLL1 genes were excised via ubiquitously expressed Cre induced by tamoxifen treatment beginning at 3 days of age (harvested at 3 weeks of age) or beginning at 4 weeks of age (harvested at 8 weeks of age). Multiple techniques, including x-ray analysis, double-labeling with calcein and alizarin red stains for measurement of dentin formation rate, and histologic and immunostaining assays, were used to analyze the dentin phenotype. RESULTS: BMP1/TLL1 double knockout mice displayed short and thin root dentin, defects in dentin mineralization, and delayed tooth eruption. Molecular mechanism studies revealed accumulation of collagens in dentin and a sharp reduction in non-collagenous proteins such as dentin matrix protein 1 and dentin sialophosphoprotein. Furthermore, we found a strong reduction in tartrate-resistant acid phosphatase, which is likely caused by defects in bone cells. CONCLUSIONS: BMP1/TLL1 appear to play crucial roles in maintaining extracellular matrix homeostasis essential to root formation and dentin mineralization.
INTRODUCTION: Mutations in the proteinasebone morphogenetic protein-1 (BMP1) were recently identified in patients with osteogenesis imperfecta, which can be associated with type 1 dentinogenesis imperfecta. BMP1 is co-expressed in various tissues and has overlapping activities with the closely related proteinasemammaliantolloid-like 1 (TLL1). In this study we investigated whether removing the overlapping activities of BMP1 and TLL1 affects the mineralization of tooth root dentin. METHODS: Floxed alleles of the BMP1 and TLL1 genes were excised via ubiquitously expressed Cre induced by tamoxifen treatment beginning at 3 days of age (harvested at 3 weeks of age) or beginning at 4 weeks of age (harvested at 8 weeks of age). Multiple techniques, including x-ray analysis, double-labeling with calcein and alizarin red stains for measurement of dentin formation rate, and histologic and immunostaining assays, were used to analyze the dentin phenotype. RESULTS:BMP1/TLL1 double knockout mice displayed short and thin root dentin, defects in dentin mineralization, and delayed tooth eruption. Molecular mechanism studies revealed accumulation of collagens in dentin and a sharp reduction in non-collagenous proteins such as dentin matrix protein 1 and dentin sialophosphoprotein. Furthermore, we found a strong reduction in tartrate-resistant acid phosphatase, which is likely caused by defects in bone cells. CONCLUSIONS:BMP1/TLL1 appear to play crucial roles in maintaining extracellular matrix homeostasis essential to root formation and dentin mineralization.
Authors: Yaroslava Ruzankina; Carolina Pinzon-Guzman; Amma Asare; Tony Ong; Laura Pontano; George Cotsarelis; Valerie P Zediak; Marielena Velez; Avinash Bhandoola; Eric J Brown Journal: Cell Stem Cell Date: 2007-06-07 Impact factor: 24.633
Authors: Yongbo Lu; Ling Ye; Shibin Yu; Shubin Zhang; Yixia Xie; Marc D McKee; Yan Chun Li; Juan Kong; J David Eick; Sarah L Dallas; Jian Q Feng Journal: Dev Biol Date: 2006-11-07 Impact factor: 3.582
Authors: Otto Baba; Chunlin Qin; Jan C Brunn; James N Wygant; Bradley W McIntyre; William T Butler Journal: Matrix Biol Date: 2004-10 Impact factor: 11.583
Authors: P V Asharani; Katharina Keupp; Oliver Semler; Wenshen Wang; Yun Li; Holger Thiele; Gökhan Yigit; Esther Pohl; Jutta Becker; Peter Frommolt; Carmen Sonntag; Janine Altmüller; Katharina Zimmermann; Daniel S Greenspan; Nurten A Akarsu; Christian Netzer; Eckhard Schönau; Radu Wirth; Matthias Hammerschmidt; Peter Nürnberg; Bernd Wollnik; Thomas J Carney Journal: Am J Hum Genet Date: 2012-04-06 Impact factor: 11.025
Authors: Barry M Steiglitz; Melvin Ayala; Karthikeyan Narayanan; Anne George; Daniel S Greenspan Journal: J Biol Chem Date: 2003-10-24 Impact factor: 5.157
Authors: Shuhei Tsuchiya; James P Simmer; Jan C-C Hu; Amelia S Richardson; Fumiko Yamakoshi; Yasuo Yamakoshi Journal: J Bone Miner Res Date: 2011-01 Impact factor: 6.741