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Function of beta1 integrin in oral epithelia and tooth bud morphogenesis.

ABSTRACT: Integrin beta1 is critical for basement membrane organization and hair follicle morphogenesis in the skin epidermis; however, less is known about its function in the developing oral epithelium. Since the skin and oral epithelia share structural similarity, we hypothesized that beta1 integrin function would be critical for the normal development of oral epithelium and tooth buds. The conditional (oral mucosa-specific) beta1 integrin knockout (KO) mice displayed severe disruption of the basement membrane of the tongue epithelium and developing tooth buds. Interestingly, unlike the developing hair follicles, early morphological development of the KO molar tooth buds was normal. However, subsequent morphogenetic events, such as cusp formation, cervical loop down-growth, and ameloblast polarization, did not occur normally. Primary KO oral keratinocytes showed defective cell spreading and robust focal adhesions. Our studies indicate that beta1 integrin plays an essential role in the normal development of the oral epithelium and its appendages.

SUBMITTER: Chen B

PROVIDER: S-EPMC2882240 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature

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Function of beta1 integrin in oral epithelia and tooth bud morphogenesis.

Chen B B Goodman E E Lu Z Z Bandyopadhyay A A Magraw C C He T T Raghavan S S

Journal of dental research 20090601 6

Integrin beta1 is critical for basement membrane organization and hair follicle morphogenesis in the skin epidermis; however, less is known about its function in the developing oral epithelium. Since the skin and oral epithelia share structural similarity, we hypothesized that beta1 integrin function would be critical for the normal development of oral epithelium and tooth buds. The conditional (oral mucosa-specific) beta1 integrin knockout (KO) mice displayed severe disruption of the basement m ...[more]

PMID: 19587159

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Project description:Whole tooth regeneration approaches currently are limited by our inability to bioengineer full-sized, living replacement teeth. Recently, decellularized organ scaffolds have shown promise for applications in regenerative medicine by providing a natural extracellular matrix environment that promotes cell attachment and tissue-specific differentiation leading to full-sized organ regeneration. We hypothesize that decellularized tooth buds (dTBs) created from unerupted porcine tooth buds (TBs) can be used to guide reseeded dental cell differentiation to form whole bioengineered teeth, thereby providing a potential off-the-shelf scaffold for whole tooth regeneration. Porcine TBs were harvested from discarded 6-mo-old pig jaws, and decellularized by successive sodium dodecyl sulfate/Triton-X cycles. Four types of replicate implants were used in this study: 1) acellular dTBs; 2) recellularized dTBs seeded with porcine dental epithelial cells, human dental pulp cells, and human umbilical vein endothelial cells (recell-dTBs); 3) dTBs seeded with bone morphogenetic protein (BMP)-2 (dTB-BMPs); and 4) freshly isolated nondecellularized natural TBs (nTBs). Replicate samples were implanted into the mandibles of host Yucatan mini-pigs and grown for 3 or 6 mo. Harvested mandibles with implanted TB constructs were fixed in formalin, decalcified, embedded in paraffin, sectioned, and analyzed via histological methods. Micro-computed tomography (CT) analysis was performed on harvested 6-mo samples prior to decalcification. All harvested constructs exhibited a high degree of cellularity. Significant production of organized dentin and enamel-like tissues was observed in dTB-recell and nTB implants, but not in dTB or dTB-BMP implants. Micro-CT analyses of 6-mo implants showed the formation of organized, bioengineered teeth of comparable size to natural teeth. To our knowledge, these results are the first to describe the potential use of dTBs for functional whole tooth regeneration.

Dataset Information

Function of beta1 integrin in oral epithelia and tooth bud morphogenesis.

Publications

Function of beta1 integrin in oral epithelia and tooth bud morphogenesis.

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