Col1a1-cre mediated activation of β-catenin leads to aberrant dento-alveolar complex formation

다국어 초록 (Multilingual Abstract)

Wnt/β-catenin signaling plays a critical role in bone formation and regeneration. Dentin and cementum share many similarities with bone in their biochemical compositions and biomechanical properties. Whether Wnt/β-catenin signaling is involved in the dento-alveolar complex formation is unknown. To understand the roles of Wnt/β-catenin signaling in the dento-alveolar complex formation, we generated conditional β-catenin activation mice through intercross of Catnb+/lox(ex3) mice with Col1a1-cre mice. In mutant mice, tooth formation and eruption was disturbed. Lower incisors and molars did not erupt. Bone formation was increased in the mandible but tooth formation was severely disturbed. Hypomineralized dentin was deposited in the crown but roots of molars were extremely short and distorted. In the odontoblasts of mutant molars, expression of dentin matrix proteins was obviously downregulated following the activation of β-catenin whereas that of mineralization inhibitor was increased. Cementum and periodontal ligament were hypoplastic but periodontal space was narrow due to increased alveolar bone formation. While cementum matrix proteins were decreased, bone matrix proteins were increased in the cementum and alveolar bone of mutant mice. These results indicate that local activation of β-catenin in the osteoblasts and odontoblasts leads to aberrant dento-alveolar complex formation. Therefore, appropriate inhibition of Wnt/β-catenin signaling is important for the dento-alveolar complex formation.

목차 (Table of Contents)

• Abstract
• Introduction
• Materials and Methods
• Results
• Discussion
• Acknowledgements
• References

참고문헌 (Reference)

1 Liu F, "Wnt/beta-catenin signaling in oral tissue development and disease" 89 : 318-330, 2010

2 Liu F, "Wnt/beta-catenin signaling directs multiple stages of tooth morphogenesis" 313 : 210-224, 2008

3 Chen J, "Wnt/beta-catenin signa ling plays an essential role in activation of odontogenic mesenchyme during early tooth development" 334 : 174-185, 2009

4 Nemoto E, "Wnt signaling inhibits cementoblast diff erentiation and promotes proliferation" 44 : 805-812, 2009

5 Reya T, "Wnt signaling in stem cells and cancer" 434 : 843-850, 2005

6 Logan CY, "The Wnt signaling pathway in development and disease" 20 : 781-810, 2004

7 Nakatomi M, "Sonic hedgehog signaling is important in tooth root development" 85 : 427-431, 2006

8 Li J, "RANK is the intrinsic hematopoietic cell surface receptor that controls osteoclastogenesis and regulation of bone mass and calcium metabolism" 97 : 1566-1571, 2000

9 Kong YY, "OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis" 397 : 315-323, 1999

10 Dacquin R, "Mouse alpha1(I)-collagen promoter is the best known promoter to driveefficient Cre recombinase expression in osteoblast" 224 : 245-251, 2002

11 Gong Y, "LDL receptor-related protein 5 (LRP5) aff ects bone accrual and eye development" 107 : 513-523, 2001

12 Harada N, "Intestinal polyposis in mice with a dominant stable mutation of the beta-catenin gene" 18 : 5931-5942, 1999

13 Boyden LM, "High bone density due to a mutation in LDL-receptor-related protein 5" 346 : 1513-1521, 2002

14 Yamashiro T, "Expression of bone morpho genetic proteins and Msx genes during root formation" 82 : 172-176, 2003

15 Holmen SL, "Essential role of beta-catenin in postnatal bone acquisition" 280 : 21162-21168, 2005

16 Steele-Perkins G, "Essential role for NFI-C/CTF transcription-replication factor in tooth root development" 23 : 1075-1084, 2003

17 Kim N, "Diverse roles of the tumor necrosis factor family member TRANCE in skeletal physiology revealed by TRANCE defi ciency and partial rescue by a lymphocyte-expressed TRANCE transgene" 97 : 10905-10910, 2000

18 Gao Y, "Disruption of Smad4 in odontoblasts causes multiple keratocystic odontogenic tumors and tooth malformation in mice" 29 : 5941-5951, 2009

19 Tiffee JC, "Dental abnormalities associated with failure of tooth eruption in src knockout and op/ op mice" 65 : 53-58, 1999

20 Jarvinen E, "Continuous tooth generation in mouse is induced by activated epithelial Wnt/beta-catenin signaling" 103 : 18627-18632, 2006

21 Kim TH, "Constitutive stabilization of β-catenin in the dental mesenchyme leads to excessive dentin and cementum formation" 412 : 549-555, 2011

22 Kato M, "Cbfa1-independent decrease in osteoblastproliferation, osteopenia, and persistent embryonic eye vascularizationin mice defi cient in Lrp5, a Wnt coreceptor" 157 : 303-314, 2002

23 Glass DA 2nd, "Canonical Wnt signaling in differentiated osteoblasts controls osteoclast diff erentiation" 8 : 751-764, 2005

24 Lu X, "A new osteopetrosis mutant mouse strain (ntl) with odontoma-like proliferations and lack of tooth roots" 117 : 625-635, 2009

25 Little RD, "A mutation in the LDL receptor-related protein 5 gene results in the autosomal dominant high-bone-mass trait" 70 : 11-19, 2002