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Inhibition of Chondrocyte Hypertrophy of Osteoarthritis by Disruptor Peptide

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Thomas Jefferson University Philadelphia United States

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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 GscAMP signaling and inhibiting GqPLC 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.

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Technical Report,01 Jul 2016,30 Jun 2017



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Approved For Public Release;

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