Nutritional deficiency induces nucleus pulposus cell apoptosis via the ATF4-PKM2-AKT signal axis

Abstract

Abstract Background The intervertebral disc is the largest avascular tissue in the human body. The nucleus pulposus (NP) consumes glucose and oxygen to generate energy to maintain cellular metabolism via nutrients that diffuse from the cartilage endplate. The microenvironment in the intervertebral disc becomes nutritionally deficient during degeneration, and nutritional deficiency has been shown to inhibit the viability and proliferation of NP cells. Methods To investigate the molecular mechanism by which nutritional deficiency reduces viability and decreases proliferation, we created an in vitro model by using decreasing serum concentration percentages. Results In this study, we found that nutritional deficiency reduced NP cell viability and increased cell apoptosis and that the upregulation of ATF4 expression and the downregulation of PKM2 expression were involved in this process. Moreover, we found that PKM2 inhibition can reduce the cell apoptosis induced by ATF4 silence under nutritional deficiency. Conclusion Our findings revealed that PKM2 inhibition reduces the cell apoptosis induced by ATF4 silence under nutritional deficiency by inhibiting AKT phosphate. Revealing the function and mechanism of NP cell development under nutritional deficiency will provide new insights into the etiology, diagnosis, and treatment of intervertebral disc and related diseases.

Keywords

• Intervertebral disc degeneration
• Nucleus pulposus
• Nutritional deficiency
• ATF4
• PKM2