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LOXL3 Inhibits Autophagy of Chondrocytes by Activating Rheb in Osteoarthritis

Guang-Ping Zheng1, Chen Liu1, Liang Zhang2

  • 1Ganzhou Municipal Key Laboratory of Bone and Joint Research, The Affiliated Ganzhou Hospital of Nanchang University, Ganzhou, 341000, China.

Current Medical Science
|December 28, 2023
PubMed
Abstract

Insights

Lysyl oxidase like 3 (LOXL3) inhibits chondrocyte autophagy in osteoarthritis by activating Rheb and mTORC1 pathways. Silencing LOXL3 or Rheb restores autophagy, suggesting therapeutic potential for OA.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Osteoarthritis Research

Background:

  • Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage breakdown.
  • Autophagy plays a crucial role in maintaining chondrocyte homeostasis.
  • Dysregulation of autophagy is implicated in OA pathogenesis.

Purpose of the Study:

  • To investigate the role of lysyl oxidase like 3 (LOXL3) in regulating chondrocyte autophagy.
  • To elucidate the specific molecular mechanisms, particularly the involvement of the Rheb/mammalian target of rapamycin complex 1 (mTORC1) pathway.

Main Methods:

  • Anterior cruciate ligament transection (ACLT) model in rats to induce OA.
  • Isolation and culture of chondrocytes.
  • Western blotting to analyze protein expression (LOXL3, Rheb, p-p70S6K, autophagy markers).
  • Immunofluorescence assay to visualize chondrocyte autophagy.

Main Results:

  • LOXL3 and Rheb protein levels were elevated in OA chondrocytes.
  • LOXL3 silencing decreased Rheb and p-p70S6K, and increased autophagy markers.
  • Rheb silencing reversed the effects of LOXL3, confirming its role.
  • Immunofluorescence confirmed LOXL3 and Rheb's impact on autophagy.

Conclusions:

  • LOXL3 inhibits chondrocyte autophagy in OA.
  • This inhibition occurs via activation of the Rheb/mTORC1 signaling pathway.
  • Targeting LOXL3 or Rheb may offer a therapeutic strategy for OA.
Keywords:
LOXL3RhebautophagychondrocytemTORC1osteoarthritis

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