Intracellular interleukin-1 receptor antagonist in osteoarthritis chondrocytes

Minako Murata, Carol Trahan, Junichi Hirahashi, Henry J. Mankin, Christine A. Towle

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)


The objective of the current study was to determine whether the balance of interleukin-1 and intracellular interleukin-1 receptor antagonist in chondrocytes in osteoarthritic human joints favors agonist action. Chondrocytes were isolated from cartilage specimens taken at the time of joint arthroplasty. Interleukin-1α, interleukin-1β, and intracellular interleukin-1 receptor antagonist messenger ribonucleic acids were assessed by reverse transcriptase-polymerase chain reaction, and chondrocyte lysates were analyzed by enzyme-linked immunosorbent assay for the respective proteins. Type I intracellular interleukin receptor antagonist transcripts were the only intracellular variant detected in osteoarthritis chondrocytes. In cartilage graded as advanced osteoarthritis both interleukin proteins in chondrocyte lysates decreased, correlating with decreased interleukin-1α and β messenger ribonucleic acids. Interleukin-1 receptor antagonist exceeded interleukin-1α in chondrocyte lysates by one order of magnitude except that in moderate osteoarthritis, antagonist was only two- to fourfold in excess. Interleukin-1α and interleukin-1β proteins were correlated closely in individual lysates, with interleukin-1β exceeding interleukin-1β by one order of magnitude. In moderately degenerated cartilage, intracellular antagonist may not be sufficiently abundant to block postulated intracellular functions of precursor interleukin-1α. Furthermore, if stored interleukin-1α, interleukin-1β, and interleukin receptor antagonist are released from chondrocytes, the localized antagonist would be insufficient to prevent signaling through cell surface receptors. Chondrocyte-derived interleukin-1α and interleukin-1β may locally overwhelm inhibition by interleukin receptor antagonist to promote the early degenerative changes in osteoarthritis.

Original languageEnglish
Pages (from-to)285-295
Number of pages11
JournalClinical Orthopaedics and Related Research
Publication statusPublished - 2003 Apr 1
Externally publishedYes

ASJC Scopus subject areas

  • Surgery
  • Orthopedics and Sports Medicine


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