Leptin Regulates Intervertebral Disc Calcification and Ossification by Promoting Glycolysis Through OCN/HIF-1α Axis.

Area of Science:

• Biochemistry
• Cell Biology
• Orthopedics

Background:

• Intervertebral disc degeneration (IDD) involves cartilage endplate (CEP) cell calcification and ossification.
• CEP cells primarily utilize glycolysis for energy metabolism during IDD.
• The precise mechanism of leptin (LEP) in IDD, particularly its link to glycolysis in CEP cells, is not fully understood.

Purpose of the Study:

• To investigate the underlying mechanism of leptin (LEP) in promoting intervertebral disc degeneration (IDD).
• To explore the role of glycolysis and the OCN/HIF-1α axis in LEP-induced CEP cell calcification and ossification.

Main Methods:

• Establishment of a rat IDD model and in vitro culture of LEP-treated CEP cells.
• Administration of a glycolysis inhibitor (2-DG) and sh-HIF-1α.
• Assessment of calcification and ossification markers (BMP-2, Sox9, OCN, Runx2, ALP activity, calcified nodules).
• Measurement of glycolysis-related proteins and lactic acid levels.

Main Results:

• LEP dose-dependently promoted CEP cell calcification and ossification, upregulating related indicators and osteogenesis markers.
• LEP increased glycolysis, evidenced by elevated glycolysis-related proteins and lactic acid, which was reversed by 2-DG.
• LEP upregulated the OCN/HIF-1α axis, and knockdown of OCN or HIF-1α inhibited LEP-induced calcification and ossification.

Conclusions:

• Leptin (LEP) is elevated in IDD and accelerates CEP cell calcification and ossification.
• LEP stimulates glycolysis via the OCN/HIF-1α axis, driving IDD progression.
• Targeting the LEP-induced glycolysis pathway presents a potential therapeutic strategy for IDD.