Inhibition of Chondrocyte Hypertrophy of Osteoarthritis by Disruptor Peptide
Abstract
The goals of this research project is to characterize how disruptor peptide blocks beta-catenin interaction with PTH receptor, inhibits chondrocyte hypertrophy and prevents osteoarthritis (OA) progression. In the first year, we completed the most work in the Aim 1 and initiated some work in Aim 2. We designed a disruptor peptide corresponding to the carboxyl-terminal region of PTH receptor, and found this disruptor peptide inhibited beta-catenin binding to PTH receptor by GST-pull down assay. We also confirmed that disruptor peptide conjugated to penetratin can enter cells. Importantly, disruptor peptide can reverse the beta-catenin-mediated PTH receptor signaling switch by increasing Gs/cAMP signaling and inhibiting Gq/PLC activation in chondrocytes. In addition, we successfully induced ATDC5 cell differentiation from proliferating chondrocytes to the hypertrophic stage, and generated mouse OA model surgically induced by destabilization of the medial meniscus. These results provide the foundation for further studies whether disruptor peptide can inhibit chondrocyte hypertrophy in vitro and protect cartilage damage in a mouse OA model.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2017
- Accession Number
- AD1046225
Entities
People
- Bin Wang
Organizations
- Thomas Jefferson University