Exogenous Parathyroid Hormone Alleviates Intervertebral Disc Degeneration through the Sonic Hedgehog Signalling Pathway Mediated by CREB

Oxidative Medicine and Cellular Longevity, vol. 2022, pp. 9955677

Abstract

As an important hormone that regulates the balance of calcium and phosphorus, parathyroid hormone (PTH) has also been found to have an important function in intervertebral disc degeneration (IVDD). Our aim was to investigate the mechanism by which PTH alleviates IVDD. In this study, the PTH 1 receptor was found to be highly expressed in severely degenerated human nucleus pulposus (NP) cells. We found in the mouse model of IVDD that supplementation with exogenous PTH alleviated the narrowing of the intervertebral space and the degradation of the extracellular matrix (ECM) caused by tail suspension (TS). In addition, inflammation, oxidative stress, and apoptosis levels were significantly increased in the intervertebral disc tissues of TS‐induced mice, and the activity of NP cells was decreased. TS also led to the downregulation of Sonic hedgehog (SHH) signalling pathway‐related signal molecules in NP cells such as SHH, Smoothened, and GLI1. However, supplementation with exogenous PTH can reverse these changes. In vitro, PTH also promotes the activity of NP cells and the secretion of ECM. However, the antagonist of the SHH signalling pathway can inhibit the therapeutic effect of PTH on NP cells. In addition, a cAMP‐response element‐binding protein, as an important transcription factor, was found to mediate the promotion of PTH on the SHH signalling pathway. Our results revealed that PTH can alleviate IVDD by inhibiting inflammation, oxidative stress, and apoptosis and improving the activity of NP cells via activating the SHH signalling pathway.

Authors 6

1. You Li Aachen Department of Trauma and Reconstructive Surgery

   RWTH Aachen University · Universitätsklinikum Aachen · Jiangsu Province Hospital

   Affiliation as printed

   Department of Orthopaedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China

   Department of Trauma and Reconstructive Surgery, RWTH Aachen University Hospital, Aachen, Germany

2. Yifan Wei

   Jiangsu Province Hospital

   Affiliation as printed

   Department of Orthopaedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China

3. He Li

   Jiangsu Province Hospital

   Affiliation as printed

   Department of Orthopaedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China

4. Dengshun Miao

   Nanjing Medical University

   Affiliation as printed

   The Research Center for Bone and Stem Cells, Department of Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, China

5. Cheng Ma corresponding

   Jiangsu Province Hospital

   Affiliation as printed

   Department of Orthopaedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China

6. Yongxin Ren corresponding

   Jiangsu Province Hospital

   Affiliation as printed

   Department of Orthopaedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China