Parathyroid hormone 1 receptor as a potential therapeutic target for intervertebral disc degeneration

Abstract

It is reported that parathyroid hormone 1 receptor (PTH1R) is crucial for intervertebral disc homeostasis maintenance. Annular tear was widely accepted as a common condition to destroy the immune privilege of the disk. To explore whether PTH1R is related to the pathogenesis of annular tear induced-intervertebral disc degeneration (IVDD) in this study, we analyzed the protein content of PTH1R in deteriorated people nucleus pulposus (NP) structure. Moreover, PTH1R activity andextracellular matrix (ECM) metabolism-related factors in the rat nucleus pulposus cells (NPCs) under oxidative stress conditions were evaluated by quantitative real-time polymerase chain reaction (RT-qPCR) in vitro. In addition, a rat IVDD model was constructed by a customized annulus needle puncture (ANP) device to evaluate IVDD grades in vivo. Immunohistochemical staining was used to detect the performance of type II collagen (Col II) and PTH1R. The results displayed that the expression of PTH1R declined in degenerated human NP tissue. The increased PTH1R activity were observed in rat NPCs with low concentration Tert-Butyl hydroperoxide (TBHP) treatment in vitro. In the rat IVDD model, the disc height had progressively narrowed and the disc structure was apparently disrupted in the ANP punctured discs. The protein expression of Col II and PTH1R was significantly down-regulated in ANP-punctured disc. This research demonstrated that our previous rat annulus needle puncture model could provide a reliable guide to the study of biologic processes in degenerating disks. Besides PTH1R has an inevitable connection with IVDD disease.