Mechanical load inhibits IL-1 induced matrix degradation in articular cartilage

P. A. Torzilli, M. Bhargava, S. Park, C. T C Chen

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Objective: Osteoarthritis is a disease process of cellular degradation of articular cartilage caused by mechanical loads and inflammatory cytokines. We studied the cellular response in native cartilage subjected to a mechanical load administered simultaneously with an inflammatory cytokine interleukin-1 (IL-1), hypothesizing that the combination of load and cytokine would result in accelerated extracellular matrix (ECM) degradation. Methods: Mature bovine articular cartilage was loaded for 3 days (stimulation) with 0.2 and 0.5 MPa stresses, with and without IL-1 (IL-1α, 10 ng/ml), followed by 3 days of no stimulation (recovery). Aggrecan and collagen loss were measured as well as aggrecan cleavage using monoclonal antibodies AF-28 and BC-3 for cleavage by aggrecanases (ADAMTS) and matrix metalloproteinases (MMPs), respectively. Results: Incubation with IL-1 caused aggrecan cleavage by aggrecanases and MMPs during the 3 days of stimulation. A load of 0.5 MPa inhibited the IL-1-induced aggrecan loss while no inhibition was found for the 0.2 MPa stress. There was no collagen loss during the treatments but upon load and IL-1 removal proteoglycan and collagen loss increased. Load itself under these conditions was found to have no effect when compared to the unloaded controls. Conclusions: A mechanical load of sufficient magnitude can inhibit ECM degradation by chondrocytes when stimulated by IL-1. The molecular mechanisms involved in this process are not clear but probably involve altered mechanochemical signal transduction between the ECM and chondrocyte.

Original languageEnglish (US)
Pages (from-to)97-105
Number of pages9
JournalOsteoarthritis and Cartilage
Volume18
Issue number1
DOIs
StatePublished - Jan 2010

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Cartilage
Articular Cartilage
Interleukin-1
Aggrecans
Collagen
Degradation
Extracellular Matrix
Signal transduction
Monoclonal antibodies
Cytokines
Chondrocytes
Matrix Metalloproteinase 3
Recovery
Proteoglycans
Matrix Metalloproteinases
Osteoarthritis
Interleukin-10
Signal Transduction
Monoclonal Antibodies
Metalloproteases

ASJC Scopus subject areas

  • Biomedical Engineering
  • Orthopedics and Sports Medicine
  • Rheumatology

Cite this

Mechanical load inhibits IL-1 induced matrix degradation in articular cartilage. / Torzilli, P. A.; Bhargava, M.; Park, S.; Chen, C. T C.

In: Osteoarthritis and Cartilage, Vol. 18, No. 1, 01.2010, p. 97-105.

Research output: Contribution to journalArticle

Torzilli, P. A. ; Bhargava, M. ; Park, S. ; Chen, C. T C. / Mechanical load inhibits IL-1 induced matrix degradation in articular cartilage. In: Osteoarthritis and Cartilage. 2010 ; Vol. 18, No. 1. pp. 97-105.
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