Related Experiment Video

Updated: Apr 19, 2026

Creation of a Knee Joint-on-a-Chip for Modeling Joint Diseases and Testing Drugs
12:44

Creation of a Knee Joint-on-a-Chip for Modeling Joint Diseases and Testing Drugs

Published on: January 27, 2023

4.7K

Effects of tofacitinib on nucleic acid metabolism in human articular chondrocytes

Hideki Koizumi1, Mitsumi Arito, Wataru Endo

  • 1Clinical Proteomics & Molecular Medicine, St. Marianna University Graduate School of Medicine , Sugao, Miyamae, Kawasaki, Kanagawa , Japan.

Modern Rheumatology
|December 16, 2014
PubMed
Abstract

Insights

Tofacitinib decreases adenosine monophosphate deaminase 2 (AMPD2) in chondrocytes, leading to increased cellular adenosine levels. This suggests a novel anti-inflammatory mechanism for tofacitinib via purine metabolism regulation.

Area of Science:

  • Biochemistry
  • Pharmacology
  • Cell Biology

Background:

  • Tofacitinib is a Janus kinase inhibitor used in treating inflammatory conditions.
  • Previous studies indicated tofacitinib reduces adenosine monophosphate deaminase 2 (AMPD2) in chondrocytes.
  • Purine metabolism plays a crucial role in cellular function and inflammation.

Purpose of the Study:

  • To confirm the effect of tofacitinib on AMPD2 expression in human articular chondrocytes and a chondrosarcoma cell line.
  • To investigate the impact of tofacitinib on purine nucleotide metabolism, specifically adenosine and AMP levels.
  • To elucidate a potential novel anti-inflammatory mechanism of tofacitinib.

Main Methods:

  • Human articular chondrocytes and OUMS-27 cells were treated with tofacitinib.
  • Western blot analysis was used to determine AMPD2 and related enzyme levels.
  • Mass spectrometry was employed to quantify cellular adenosine and AMP levels.

Main Results:

  • Tofacitinib significantly decreased AMPD2 levels in chondrocytes (p = 0.025).
  • While not statistically significant, adenosine kinase and 5'-nucleotidase levels showed a decreasing trend.
  • Tofacitinib significantly reduced cellular adenosine levels in OUMS-27 cells (p = 0.014) and increased AMP levels (p = 0.066).

Conclusions:

  • Tofacitinib downregulates AMPD2, leading to increased cellular adenosine levels.
  • Elevated adenosine, known for its anti-inflammatory properties, represents a novel functional aspect of tofacitinib.
  • These findings provide insights into the pharmacological effects of tofacitinib on purine metabolism and inflammation.
Keywords:
AMP deaminaseAdenosineChondrocytesTofacitinib

More Related Videos

Software-Assisted Quantitative Measurement of Osteoarthritic Subchondral Bone Thickness08:52

Software-Assisted Quantitative Measurement of Osteoarthritic Subchondral Bone Thickness

Published on: March 18, 2022

3.6K
Scaled-Up Preparation of an Intermediate of Upatinib, ACT051-308:36

Scaled-Up Preparation of an Intermediate of Upatinib, ACT051-3

Published on: April 7, 2023

1.7K

Related Concept Videos

TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
11.1K
Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF01:24

Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF

Tumor Necrosis Factor (TNF), a proinflammatory cytokine, contributes significantly to the inflammation seen in Crohn's disease. It exists as soluble TNF and membrane-bound TNF, with actions mediated through TNF receptors (TNFR). TNFR activation leads to the release of proinflammatory cytokines, T-cell activation, collagen production, and leukocyte migration, all contributing to inflammation in Crohn's disease. Anti-TNF monoclonal antibodies, namely infliximab (Remicade), adalimumab...
824
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
10.9K
Inhibitors of Bacterial DNA Synthesis01:28

Inhibitors of Bacterial DNA Synthesis

Bacterial pathogens depend on precise and efficient DNA replication to sustain infection. Two type II topoisomerases—DNA gyrase and topoisomerase IV—are critical to this process, as they resolve DNA supercoiling and unlink chromosomes during replication. Fluoroquinolones, synthetic derivatives of quinolones, exploit this mechanism by stabilizing the transient DNA–enzyme cleavage complex, preventing strand religation, and causing lethal double-strand breaks. These...
94
Bioactivation and Tissue Toxicity01:25

Bioactivation and Tissue Toxicity

Bioactivation is a metabolic process that transforms less reactive substances into highly reactive metabolites, initiating tissue toxicity. This transformation can lead to various toxic effects, including carcinogenesis and teratogenesis. Reactive metabolites are classified into two main types: electrophiles and free radicals.Electrophiles are electron-deficient species and are produced primarily by the enzyme cytochrome P-450 during the metabolism of compounds containing carbon, nitrogen, or...
137
Inhibitors of Viral Protein Synthesis01:30

Inhibitors of Viral Protein Synthesis

Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...
47