Use of a stringent dimerizer-regulated gene expression system for controlled BMP2 delivery.

Use of a stringent dimerizer-regulated gene expression system for controlled BMP2 delivery. Research Abstract Details 

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Use of a stringent dimerizer-regulated gene expression system for controlled BMP2 delivery. Abstract Text:

Jeong-Tae Koh,Chunxi Ge,Ming Zhao,Zhuo Wang,Paul H Krebsbach,Zhuoran Zhao,Renny T Franceschi,

Gene therapy using constitutively active viral promoters to drive expression of bone morphogenetic proteins (BMPs) has been extensively evaluated as a strategy for inducing bone regeneration. However, this approach offers little control over the concentration, timing, or duration of BMP synthesis. To gain greater control over BMP kinetics, we developed a new inducible system for the controlled expression of BMP2 using a two-component transcription factor that is dimerized with rapamycin (Rap). This approach provided stringent control over BMP2 synthesis with no BMP expression detected in the uninduced state. Rapamycin or the less immunosuppressive analogue, AP21967, rapidly and reversibly induced BMP2 in a dose-dependent manner (range 0.1-10 nM). Subcutaneous implants of fibroblasts containing the Rap-inducible system in syngeneic C57BL/6 mice were highly responsive to ip Rap injection (0.1-1 mg/kg). Peak BMP2 levels were detected within 24 h of a single Rap injection and declined to undetectable levels after 8-10 days. Alternate-day Rap injections (1 mg/kg) for 6 weeks induced subcutaneous ectopic bone formation. Rap-dependent healing of a critical-sized cranial defect was also achieved using this system. This regulated BMP2 expression system will be extremely useful for examining the role of timing and sequence of BMP delivery on bone regeneration.

Use of a stringent dimerizer-regulated gene expression system for controlled BMP2 delivery. Publishing Authors By Initials

JT Koh,C Ge,M Zhao,Z Wang,PH Krebsbach,Z Zhao,RT Franceschi,

For similar peptides: intercellular signaling peptides and proteins: cytokines: transforming growth factor beta research abstracts see: peptides: intercellular signaling peptides and proteins: cytokines: transforming growth factor beta research

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Use of a stringent dimerizer-regulated gene expression system for controlled BMP2 delivery. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Molecular therapy : the journal of the American So

VOLUME: 14

Page Numbers: 684-91

Journal Abbreviation: Mol. Ther.

ISSN: 1525-0016

DAY: 14

MONTH: 08

YEAR: 2006

Use of a stringent dimerizer-regulated gene expression system for controlled BMP2 delivery. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 100890581

Use of a stringent dimerizer-regulated gene expression system for controlled BMP2 delivery. Keywords Mesh Terms:

KEYWORDS: Transforming Growth Factor beta

MESH TERMS: metabolism

Chemical & Substance for Abstract: Use of a stringent dimerizer-regulated gene expression system for controlled BMP2 delivery. Information

Substance Name: Sirolimus

Registry Number: 53123-88-9

Grant and Affiliation Information for Use of a stringent dimerizer-regulated gene expression system for controlled BMP2 delivery.

AFFILIATION: Department of Periodontics and Oral Medicine, School of Dentistry, and Center for Craniofacial Regeneration, School of Medicine, University of Michigan, Ann Arbor, MI 48109, USA.

Country: United States

AGENCY: United States NIDCR

GRANT: DE13386

ACRONYM: DE

MEDLINETA: Mol Ther

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