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Leptin downregulates aggrecan through the p38-ADAMST pathway in human nucleus pulposus cells

Zheng Li1, Xin Yu2, Jinqian Liang1

  • 1Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China.

Plos One
|October 10, 2014
PubMed

Insights

Obesity hormone leptin upregulates aggrecan-degrading enzymes (ADAMTS-4/5) via p38 in human disc cells, driving intervertebral disc degeneration (IDD). This reveals a key mechanism in obesity-related IDD.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Orthopedics

Background:

  • Obesity is linked to intervertebral disc degeneration (IDD), but mechanisms are unclear.
  • Aggrecan degradation by ADAMTS-4 and ADAMTS-5 is implicated in IDD.
  • Leptin levels are elevated in obesity.

Purpose of the Study:

  • Investigate leptin's effect on aggrecan and ADAMTS expression in human nucleus pulposus (NP) cells.
  • Elucidate the role of p38 signaling in leptin-induced aggrecan degradation.

Main Methods:

  • Primary human NP cells were treated with leptin.
  • Real-time PCR and Western blots assessed gene and protein expression.
  • p38 phosphorylation was analyzed.
  • Inhibitors (SB203580) and siRNAs (ADAMTS-4/5) were used to probe signaling pathways.

Main Results:

  • Leptin increased ADAMTS-4 and ADAMTS-5 mRNA and protein expression.
  • Leptin reduced aggrecan levels in NP cells.
  • Leptin induced p38 phosphorylation.
  • p38 inhibition abolished leptin's effects.
  • ADAMTS-4/5 knockdown attenuated aggrecan degradation.

Conclusions:

  • Leptin upregulates ADAMTS-4 and ADAMTS-5 via p38 activation in human NP cells.
  • This leads to increased aggrecan degradation.
  • Provides mechanistic insight into obesity-associated IDD.

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