Pharmacological inhibition of mTORC1 activity protects against inflammation-induced apoptosis of nucleus pulposus cells

• Published in: Brazilian journal of medical and biological research Vol. 54; no. 5; p. e10185
• Main Authors: Chen, Rigao, Yang, Fei, Wang, Yong, Wang, Xinling, Fan, Xiaohong
• Format: Journal Article
• Language: English
• Published: Brazil Associacao Brasileira de Divulgacao Cientifica (ABDC) 01.01.2021; Revista Brasileira de Pesquisas Medicas; Associação Brasileira de Divulgação Científica
• Subjects: Acid production; Apoptosis; BIOLOGY; Cell survival; Cytokines; Degeneration; Development and progression; Dextrose; Glucose; Glucose metabolism; Homeostasis; Humans; Inflammation; Inflammation - drug therapy; Intervertebral disc degeneration; Intervertebral Disc Degeneration - drug therapy; Intervertebral discs; Lactic acid; Mechanistic Target of Rapamycin Complex 1; MEDICINE, RESEARCH & EXPERIMENTAL; Metabolism; Metabolomics; mTORC1; Nucleus Pulposus; Nucleus pulposus cells; Physiological aspects; China; Intervertebral disc degeneration; Lactic acid; mTORC1; Nucleus pulposus cells; Apoptosis
• ISSN: 0100-879X; 1414-431X; 1414-431X; 1678-4510
• DOI: 10.1590/1414-431x202010185

Lumbar disc herniation is a common disease characterized by the degeneration of intervertebral discs (IVDs), accompanied by imbalance of metabolic and inflammatory homeostasis. Current studies establish that IVD degeneration is induced by increased apoptosis of nucleus pulposus (NP) cells. However, the underlying mechanisms of NP cell survival/apoptosis are not well elucidated. Here, we reveal a novel mechanism by which mTORC1 signaling controls NP cell survival through regulating metabolic homeostasis. We demonstrated that hyperactivated mTORC1 activity induced by inflammatory cytokines engenders the apoptosis of NP cells, whereas pharmacological inhibition of mTORC1 activity promotes NP cell survival. Using an integrative approach spanning metabolomics and biochemical approaches, we showed that mTORC1 activation enhanced glucose metabolism and lactic acid production, and therefore caused NP cell apoptosis. Our study identified mTORC1 in NP cells as a novel target for IVD degeneration, and provided potential strategies for clinical intervention of lumbar disc herniation.