Intracellular interleukin-1 receptor antagonist in osteoarthritis chondrocytes.
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-1alpha, interleukin-1beta, 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-1alpha and beta messenger ribonucleic acids. Interleukin-1 receptor antagonist exceeded interleukin-1alpha in chondrocyte lysates by one order of magnitude except that in moderate osteoarthritis, antagonist was only two- to fourfold in excess. Interleukin-1alpha and interleukin-1beta proteins were correlated closely in individual lysates, with interleukin-1beta exceeding interleukin-1beta by one order of magnitude. In moderately degenerated cartilage, intracellular antagonist may not be sufficiently abundant to block postulated intracellular functions of precursor interleukin-1alpha. Furthermore, if stored interleukin-1alpha, interleukin-1beta, and interleukin receptor antagonist are released from chondrocytes, the localized antagonist would be insufficient to prevent signaling through cell surface receptors. Chondrocyte-derived interleukin-1alpha and interleukin-1beta may locally overwhelm inhibition by interleukin receptor antagonist to promote the early degenerative changes in osteoarthritis.
Murata
Minako
M
Orthopaedic Research Laboratories, Department of Orthopaedic Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Trahan
Carol
C
Hirahashi
Junichi
J
Mankin
Henry J
HJ
Towle
Christine A
CA
D000368:Aged; D018501:Antirheumatic Agents / Q000032:analysis*; D019644:Arthroplasty, Replacement, Hip; D019645:Arthroplasty, Replacement, Knee; D019902:Chondrocytes / Q000473:pathology*; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000032:analysis* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015207:Osteoarthritis, Hip / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D020370:Osteoarthritis, Knee / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D012333:RNA, Messenger / Q000032:analysis* / Q000235:genetics*; D017472:Receptors, Interleukin-1 / Q000032:analysis* / Q000037:antagonists & inhibitors* / Q000235:genetics; D012795:Sialoglycoproteins / Q000032:analysis* / Q000235:genetics*
D018501:Antirheumatic Agents; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins