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Spermidine activates RIP1 deubiquitination to inhibit TNF-α-induced NF-κB/p65 signaling pathway in osteoarthritis

Zhong Chen1, Chuang-Xin Lin1,2, Bin Song1

  • 1Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, P. R. China.

Cell Death & Disease
|July 8, 2020
PubMed

Insights

Spermidine, a natural compound, was found to delay osteoarthritis progression in mouse models by reducing inflammation. It works by inhibiting the TNF-α-induced NF-κB pathway through RIP1 deubiquitination in fibroblast-like synoviocytes.

Area of Science:

  • Biochemistry
  • Immunology
  • Rheumatology

Background:

  • Osteoarthritis (OA) is a degenerative joint disease characterized by inflammation.
  • Spermidine is known to inhibit pro-inflammatory cytokines, but its effects on OA are not well-documented.

Purpose of the Study:

  • To investigate the potential anti-inflammatory effects of spermidine on osteoarthritis progression.
  • To explore the underlying molecular mechanisms of spermidine's action in OA models.

Main Methods:

  • Utilized anterior cruciate ligament transection (ACLT) and TNF-α induced arthritis (TIA) mouse models.
  • Administered spermidine via intraperitoneal injection (i.p.).
  • Investigated spermidine's effect on human fibroblast-like synoviocytes (H-FLS) and TNF-α-induced NF-κB/p65 signaling.

Main Results:

  • Spermidine treatment significantly attenuated synovitis, cartilage degeneration, and osteophyte formation in OA mouse models.
  • Spermidine treatment led to lower Osteoarthritis Research Society International (OARSI) and TNF-α scores.
  • Spermidine activated CYLD-mediated RIP1 deubiquitination, inhibiting TNF-α-induced NF-κB/p65 signaling in H-FLS without affecting cell viability or proliferation.

Conclusions:

  • Spermidine effectively attenuates osteoarthritis progression in mouse models.
  • The mechanism involves the inhibition of the TNF-α-induced NF-κB pathway via RIP1 deubiquitination in fibroblast-like synoviocytes.
  • Dietary spermidine intake may represent a potential therapeutic strategy for preventing osteoarthritis.

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