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OSTF1 knockdown mitigates IL-1β-induced chondrocyte injury via inhibiting the NF-κB signaling pathway

Bin Hu1, Gongwen Du2

  • 1Department of Hand and Foot Surgery, Yijishan Hospital of Wannan Medical College, No. 2, Zheshan West Road, Wuhu, Anhui, China.

Heliyon
|May 3, 2024
PubMed

Insights

Osteoclast stimulating factor 1 (OSTF1) is elevated in osteoarthritis. Reducing OSTF1 levels alleviates inflammation and cell death in chondrocytes by inhibiting the NF-κB signaling pathway, offering a potential therapeutic target for osteoarthritis.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Pathology

Background:

  • Osteoarthritis (OA) is a degenerative joint disease with unclear molecular mechanisms.
  • Osteoclast stimulating factor 1 (OSTF1), a protein involved in bone remodeling, has an unknown role in OA pathogenesis.
  • Interleukin-1β (IL-1β) is a key inflammatory mediator in OA-induced chondrocyte damage.

Purpose of the Study:

  • To investigate the role of OSTF1 in osteoarthritis.
  • To elucidate the molecular mechanisms by which OSTF1 influences IL-1β-induced chondrocyte injury.
  • To explore OSTF1's involvement in the NF-κB signaling pathway in OA.

Main Methods:

  • Established an anterior cruciate ligament transection (ALCT) rat model for osteoarthritis.
  • Quantified OSTF1 expression in human and rat cartilage tissues.
  • Performed loss-of-function assays (OSTF1 knockdown) to assess effects on IL-1β-induced chondrocyte apoptosis, inflammation, and extracellular matrix degradation.
  • Utilized transcriptomic analysis and bioinformatics to identify OSTF1-regulated genes and their overlap with NF-κB targets.

Main Results:

  • OSTF1 expression was significantly increased in the cartilage of OA patients and OA rats.
  • OSTF1 knockdown attenuated IL-1β-induced chondrocyte apoptosis, evidenced by reduced cleaved caspase-3 and cleaved PARP.
  • OSTF1 knockdown inhibited IL-1β-induced inflammation and extracellular matrix degradation in chondrocytes.
  • Transcriptomic analysis revealed OSTF1 regulates genes involved in the NF-κB signaling pathway, and OSTF1 knockdown suppressed IL-1β-activated NF-κB signaling.
  • Bioinformatics analysis confirmed an overlap between OSTF1-regulated genes and NF-κB downstream targets.

Conclusions:

  • OSTF1 plays a critical role in mediating IL-1β-induced chondrocyte injury in osteoarthritis.
  • OSTF1 knockdown mitigates OA progression by inhibiting the NF-κB signaling pathway.
  • Targeting OSTF1 presents a potential therapeutic strategy for managing osteoarthritis.
Keywords:
ApoptosisChondrocyteExtracellular matrix degradationIL-1βInflammationNF-κB signaling pathwayOSTF1Osteoarthritis

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