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17β-estradiol activates mTOR in chondrocytes by AKT-dependent and AKT-independent signaling pathways

Yulei Tao1, Haibiao Sun2, Hongyan Sun3

  • 1First Clinical Medical College, Shanxi Medical University Shanxi, China.

International Journal of Clinical and Experimental Pathology
|February 18, 2016
PubMed

Insights

17β-estradiol (E2) activates the mammalian target of rapamycin (mTOR) signaling pathway in chondrocytes. This activation occurs through both AKT-dependent and independent mechanisms, influencing matrix metalloproteinase (MMP) levels.

Area of Science:

  • Cell Biology
  • Endocrinology
  • Biochemistry

Background:

  • Chondrocytes play a crucial role in cartilage maintenance.
  • The mammalian target of rapamycin (mTOR) signaling pathway is vital in cellular processes.
  • 17β-estradiol (E2) is a key hormone with potential roles in chondrocyte function.

Purpose of the Study:

  • To investigate if 17β-estradiol (E2) activates the mTOR signaling pathway in chondrocytes.
  • To elucidate the specific mechanisms by which E2 activates mTOR in these cells.
  • To determine the downstream effects of E2-mediated mTOR activation on matrix metalloproteinase (MMP) expression.

Main Methods:

  • Utilized human immortalized chondrocyte cell lines (TC28a2 and C28/I2).
  • Treated cells with E2, PI3K inhibitor (LY294002), mTOR inhibitor (rapamycin), or combinations thereof.
  • Assessed protein levels of p-S6K1 and p-AKT via Western blot.
  • Quantified MMP3 and MMP13 mRNA levels using qRT-PCR.
  • Confirmed ERα and mTOR interaction using co-immunoprecipitation and Western blot.

Main Results:

  • E2 significantly increased p-S6K1 and p-AKT protein levels in chondrocytes.
  • E2 reversed the inhibitory effect of LY294002 on p-S6K1 levels.
  • E2 inhibited mRNA levels of MMP3 and MMP13 through the mTOR pathway.
  • ERα was found to interact with mTOR upon E2 treatment.

Conclusions:

  • E2 activates the mTOR signaling pathway in chondrocytes.
  • E2 activates mTOR via both AKT-dependent and AKT-independent pathways.
  • E2-mediated mTOR activation suppresses the expression of MMP3 and MMP13 in chondrocytes, suggesting a role in cartilage homeostasis.
Keywords:
17β-estradiolAKT-dependent and AKT-independent pathwayschondrocytesmTOR

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