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Published on: March 29, 2018
Use of a stringent dimerizer-regulated gene expression system for controlled BMP2 delivery
Jeong-Tae Koh1, Chunxi Ge, Ming Zhao
1Department of Periodontics and Oral Medicine, School of Dentistry, and Center for Craniofacial Regeneration, School of Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
Summary
A novel inducible system offers precise control over bone morphogenetic protein 2 (BMP2) synthesis using rapamycin. This breakthrough enables controlled bone regeneration and study of BMP delivery timing.
Area of Science:
- Regenerative Medicine
- Biotechnology
- Molecular Biology
Background:
- Constitutively active viral promoters for bone morphogenetic proteins (BMPs) are used for bone regeneration but lack control.
- Limited control over BMP synthesis concentration, timing, and duration hinders therapeutic applications.
Purpose of the Study:
- Develop a novel inducible system for controlled bone morphogenetic protein 2 (BMP2) expression.
- Investigate the efficacy of this system in inducing bone regeneration and ectopic bone formation.
Main Methods:
- Engineered a two-component transcription factor system dimerized by rapamycin (Rap) for inducible BMP2 expression.
- Utilized fibroblasts containing the Rap-inducible system in syngeneic C57BL/6 mice.
- Administered Rap or AP21967 to induce BMP2 expression and assessed bone formation.
Main Results:
- The system demonstrated stringent, rapamycin-dependent control over BMP2 synthesis with no expression in the uninduced state.
- BMP2 expression was rapidly and reversibly induced in a dose-dependent manner (0.1-10 nM) by Rap or AP21967.
- Successful induction of subcutaneous ectopic bone formation and healing of critical-sized cranial defects were achieved.
Conclusions:
- This regulated BMP2 expression system provides precise control over BMP kinetics.
- It is a valuable tool for studying the impact of BMP delivery timing and sequence on bone regeneration.
- The system holds significant potential for advancing bone regenerative therapies.
