Cathepsin K regulates adipocyte differentiation: possible involvement of type I collagen degradation

Endocr J. 2009;56(1):55-63. doi: 10.1507/endocrj.k08e-143. Epub 2008 Oct 8.

Abstract

We previously found that cathepsin K (CTSK) played an important role in adipocyte differentiation. However, the underlying molecular mechanism is not clear. Through the time window study, it was observed that CTSK activities were required mainly in the early phases of adipogenic process. At the same time, the expression of type I collagen disappeared. However, type I collagen can still be observed during the whole process when the CTSK inhibitor-E64 was added. The mRNA levels of peroxisome proliferator-activated receptor gamma (PPAR-gamma) and CCAAT/enhancer binding protein alpha (C/EBP-alpha) was also declining. These imply that CTSK may play a role in adipogenesis in early differentiation phases and produce an effect at least partly by degrading type I collagen, which may provides a basis for developing novel therapeutic approaches to treat obesity and the diseases associated with it.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / drug effects
  • Adipocytes / metabolism
  • Adipocytes / physiology*
  • Adipogenesis / drug effects
  • Adipogenesis / genetics
  • Animals
  • CCAAT-Enhancer-Binding Proteins / genetics
  • CCAAT-Enhancer-Binding Proteins / metabolism
  • Cathepsin K
  • Cathepsins / antagonists & inhibitors
  • Cathepsins / physiology*
  • Cell Differentiation* / drug effects
  • Cell Differentiation* / genetics
  • Collagen Type I / metabolism*
  • Collagen Type I / physiology
  • Cysteine Proteinase Inhibitors / pharmacology
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / metabolism
  • Gene Expression Regulation / drug effects
  • Leucine / analogs & derivatives
  • Leucine / pharmacology
  • Mice
  • PPAR gamma / genetics
  • PPAR gamma / metabolism
  • Protein Processing, Post-Translational / drug effects
  • Protein Processing, Post-Translational / physiology*
  • Time Factors

Substances

  • CCAAT-Enhancer-Binding Proteins
  • CEBPA protein, mouse
  • Collagen Type I
  • Cysteine Proteinase Inhibitors
  • PPAR gamma
  • Cathepsins
  • Cathepsin K
  • Ctsk protein, mouse
  • Leucine
  • E 64