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Per2 attenuates LPS-induced chondrocyte injury through the PTEN/PI3K/Akt signalling pathway

Yu Zhao1, Ding Ma1, Bingchen Dong1

  • 1Depatment of Orthopaedics, Xi'an Ninth Hospital, Xi'an 710054, Shaanxi Province, PR China.

Bioscience Reports
|May 20, 2020
PubMed

Insights

Period circadian clock 2 (Per2) plays a key role in osteoarthritis (OA) by promoting cell proliferation and inhibiting apoptosis and inflammation. Per2 activates the PTEN/PI3K/Akt pathway, suggesting it as a therapeutic target for OA.

Area of Science:

  • Molecular Biology
  • Chronobiology
  • Osteoarthritis Research

Background:

  • Osteoarthritis (OA) is a degenerative joint disease with complex mechanisms.
  • The role of circadian clock genes, such as period circadian clock 2 (Per2), in OA pathogenesis is not fully understood.

Purpose of the Study:

  • To investigate the function of Per2 in osteoarthritis.
  • To elucidate the molecular mechanisms underlying Per2's role in OA, particularly its interaction with the PTEN/PI3K/Akt signaling pathway.

Main Methods:

  • Reduced Per2 expression in human chondrocytes (NHAC-kn) using lipopolysaccharide (LPS).
  • Manipulated Per2 levels using pcDNA3.1-Per2 (overexpression) and si-Per2 (knockdown).
  • Assessed cell proliferation (MTT assay), apoptosis, inflammation (ELISA), and protein interactions (CO-IP).
  • Investigated the PTEN/PI3K/Akt pathway activation using IGF-1.

Main Results:

  • LPS treatment decreased Per2 mRNA and protein levels in NHAC-kn cells.
  • Per2 overexpression enhanced cell proliferation, inhibited apoptosis, and reduced inflammation.
  • Per2 specifically bound to PTEN, activating the PTEN/PI3K/Akt signaling pathway.
  • Per2's anti-inflammatory effects in LPS-stimulated cells were mediated via this pathway.

Conclusions:

  • Per2 plays a protective role in osteoarthritis by promoting chondrocyte proliferation and suppressing apoptosis and inflammation.
  • Per2 exerts its effects by activating the PTEN/PI3K/Akt signaling pathway.
  • Per2 represents a potential novel therapeutic target for osteoarthritis treatment.
Keywords:
PTEN/PI3K/AktPer2chondrocyteinflammationosteoarthritis

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