Blocking TNFα attenuates progressive cartilage matrix degradation in inflammatory arthritis

JINSUNG PARK, HYOSUN PARK, YOUNG LIM LEE, SUBIN WEON, YONG GIL KIM, JAE HYUK YANG, BORA NAM, SUNGSIN JO, TAE HWAN KIM

Research output: Contribution to journalArticlepeer-review

Abstract

Because damage to hyaline cartilage is irreversible, relieving progressive cartilage destruction is an important therapeutic approach for inflammatory arthritis. In the present study, human hyaline chondrocytes were isolated from total knee replacements of 15 patients with osteoarthritis (OA) and three with rheumatoid arthritis (RA). Synovial fluid of OA (n=25) and RA (n=34) were collected to measure tumor necrosis factor α (TNFα) using ELISA. Consistent with previous studies, the synovial fluid exhibited high TNFα levels and hyaline cartilage was severely destroyed in patients with RA. TNFα-treated chondrocytes were used as model for inflammatory arthritis. TNFα did not influence proliferation or extracellular matrix expression in chondrocytes, but induced matrix metalloproteinase (MMP)1, 3 and 13 expression levels in chondrocytes, which was accompanied by activation of nuclear factor-κB signaling. During chondrogenic differentiation, TNFα attenuated mRNA expression levels of anabolic factors (collagen type 2 and aggrecan) and enhanced mRNA expression of catabolic factors (MMP1, MMP3 and MMP13) in chondrocytes. Moreover, anti-TNFα agents (Golimumab) inhibited the TNFα-induced metabolic shift in chondrocytes and chondrogenic differentiation. The present study revealed a mechanism by which TNFα may induce metabolic shift in chondrocytes, leading to progressive chondrocyte destruction.

Original languageEnglish
Article number10240
JournalExperimental and Therapeutic Medicine
Volume22
Issue number2
DOIs
StatePublished - 2021 Aug

Keywords

  • Anti-TNFα inhibitor
  • Chondrocytes
  • Chondrogenic differentiation
  • Inflammatory arthritis
  • Metabolic shift
  • TNFα

Fingerprint

Dive into the research topics of 'Blocking TNFα attenuates progressive cartilage matrix degradation in inflammatory arthritis'. Together they form a unique fingerprint.

Cite this