Parecoxib prevents nucleus pulposus cells apoptosis by suppressing endoplasmic reticulum stress

C.-H. Yang, W.-L. Qi, C.-W. Zhao, W.-J. Cai, Q. Gong, J.-Y. Niu, W.-H. Zhao, L. Xu

Department of Orthopedics, Dongzhimen Hospital of Beijing University of Chinese Medicine, Beijing, China. xulinguke@163.com

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• Pharmacology

OBJECTIVE: Intervertebral disc degeneration (IVDD) is the main cause of spine diseases, and apoptosis of nucleus pulposus (NP) cells is an important risk factor for the degeneration of intervertebral discs. Endoplasmic reticulum (ER) stress is involved in multiple apoptosis processes. This study investigated whether the specific COX-2 inhibitor parecoxib can inhibit NP cell apoptosis induced by ER stress.

PATIENTS AND METHODS: Human NP cells were isolated from the disc tissue collected from IVDD patients. We used IL-1β to establish an NP cell degenerated model. Degenerated levels were detected by the analysis of cell viability, collagen II, collagen X, aggrecan, TNF-α, IL-6, and MMP-13 expression. ER stress status was examined by GRP78 and CHOP expression. Apoptosis level was mainly indicated by the positive apoptotic cells and caspase-12 expression. CHOP-plasmid transfection was performed to overexpress the CHOP protein level.

RESULTS: IL-1β could induce the decrease of viability, collagen Ⅱ, aggrecan, but an increase of collagen X, TNF-α, IL-6, and MMP-13 in NP cells, as well as the upregulation of GRP78/PERK/caspase-12 and apoptosis level, which could be inhibited by parecoxib. Parecoxib could also suppress CHOP caused by COX-2 upregulation and apoptosis in NP cells.

CONCLUSIONS: Parecoxib is a safe and efficient COX-2 inhibitor to NP cells, which could prevent NP cells apoptosis by suppressing ER stress.

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