Parathyroid hormone 1‑34 inhibits senescence in rat nucleus pulposus cells by activating autophagy via the m‑TOR pathway

Wang,Xiao‑Ying; Jiao,Li‑Yan; He,Jing‑Lan; Fu,Zhi‑An; Guo,Ru‑Jun

doi:10.3892/mmr.2018.9229

Parathyroid hormone 1‑34 inhibits senescence in rat nucleus pulposus cells by activating autophagy via the m‑TOR pathway

Authors:
- Xiao‑Ying Wang
- Li‑Yan Jiao
- Jing‑Lan He
- Zhi‑An Fu
- Ru‑Jun Guo
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Affiliations: Department of Orthopedic Surgery, The Affiliated Hospital of Hebei University of Engineering, Handan, Hebei 056002, P.R. China, Department of Dermatology, The Affiliated Hospital of Hebei University of Engineering, Handan, Hebei 056002, P.R. China, Second Department of Orthopedic Surgery, Wu'an First People's Hospital, Handan, Hebei 056300, P.R. China
Published online on: June 27, 2018 https://doi.org/10.3892/mmr.2018.9229
Pages: 2681-2688
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Osteoporosis is closely associated with intervertebral disc degeneration. While parathyroid hormone (PTH) 1‑34, which is an established drug used to treatosteoporosis, is thought to inhibit the disc degeneration associated with osteoporosis, the precise mechanism involved remains unclear. In the present study, primary Sprague‑Dawley rat nucleus pulposus cells (NPCs) were cultured, phenotyped and then treated with dexamethasone (DXM) for 48 h. Cell area analysis and β‑galactosidase staining were used to investigate the effect of DXM on the senescence of NPCs. In addition, the protein levels of LC3‑II, Beclin‑1, P62, p‑mTOR and p‑p70S6k were determined by western blotting and analyzing the regulatory effect of PTH upon autophagy and the mTOR signaling pathway in cells treated with DXM. Following autophagic inhibition induced by ATG5 siRNA transfection, the regulatory effect of PTH on senescence in NPCs were investigated in addition to the potential role of autophagy. As the concentration of DXM increased, the size of the NPCs was significantly enlarged and the proportion of cells with positive β‑galactosidase staining increased significantly (P<0.05). In terms of protein expression, PTH treatment led to an increase in LC3‑II and Beclin‑1 proteins, a reduction in P62 protein, and inhibited p‑mTOR and p‑p70S6k protein expression in DXM‑treated NPCs (P<0.05). PTH attenuated the effect of DXM according to the cell size and percentage of β‑galactosidase‑positive cells. However, the inhibition of autophagy via ATG5 siRNA transfection reversed the protective effect of PTH on cell senescence (P<0.05). Collectively, the present findings suggest that PTH may inhibit the senescence of NPCs induced by DXM by activating autophagy via the mTOR pathway.

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