Z. Pan (Hangzhou, CN)
Zhejiang University Department of Sports MedicinePresenter Of 1 Presentation
18.3.6 - Therapeutic effects of gefitinib-encapsulated thermosensitive injectable hydrogel in intervertebral disc degeneration
Abstract
Purpose
Intervertebral disc (IVD) degeneration is one of the most widespread musculoskeletal diseases world- wide, which remains an intractable clinical challenge. The aim of this study is to investigate the thera- peutic potential of the small molecule gefitinib (an epidermal growth factor receptor (EGFR) inhibitor) in ameliorating IVD degeneration.
Methods and Materials
MRI and histological staining were performed to confirm degeneration of the rat and human IVDs. To investigate the functions of EGFR in IVD pathogenesis, we created an inducible Egfr deletion system using Col2a1-CreERT2; Egfrf/f mice. We next evaluated the effect of pharmacological inhibition of EGFR signaling with gefitinib on IVD degeneration. Puncture-induced rat IVD degeneration model was established to evaluate the therapeutic effect of gefitinib-encapsulated ther- mosensitive injectable hydrogel in vivo.
Results
Aberrant EGFR activation levels were detected in both human and rat degenerative IVDs, which prompted us to investigate the functional roles of EGFR by utilizing inducible cartilage-specific EGFR-deficient mice. We demonstrated that conditional EGFR deletion in mice increased nucleus pulposus (NP) extracellular matrix (ECM) production and autophagy marker activation while MMP13 expression decreased. These outcomes are comparable to the use of a controlled-release injectable thermosensitive hydrogel of gefitinib to block EGFR activity in a puncture-induced rat model. We also conducted a case series study involving patients with non-small cell lung cancer and IVD degeneration who received gefitinib treatment from 2010 to 2015. Gefitinib-treated patients displayed a relative slower disc degenerating progression, in contrast to control subjects.
Conclusion
These findings thus provide evidence that suppression of EGFR by the FDA-approved drug gefitinib can protect IVD degeneration in rats, implying the potential application of gefitinib as a small molecule drug for treating IVD degeneration.