The role of nitric oxide in proteoglycan turnover by bovine articular cartilage organ cultures

M. Stefanovic-Racic, T. I. Morales, D. Taskiran, L. A. McIntyre, Christopher H Evans

Research output: Contribution to journalArticle

99 Citations (Scopus)

Abstract

Monolayer cultures of articular chondrocytes synthesize large amounts of nitric oxide (NO) following exposure to IL-1. The latter has antianabolic and procatabolic activities on these cells, but little is known about the role, if any, of NO in the integrated metabolic pathways of the chondrocyte. In the present study, the role of endogenously produced NO in both the synthesis and degradation of proteoglycans was investigated for the first time. Bovine articular cartilage slices exposed to 20 U/ml human rIL-1β (hrIL-1β) synthesized large amounts of NO for 1 to 2 days, after which production fell to a steady state level ~20% of the peak value for the remainder of the 14- day incubation. The NO synthase inhibitor, N-monomethyl L-arginine (L-NMA, 1 mM), blocked NO production and enhanced the acute catabolic effects of hrIL- 1β in cartilage derived from both calves and adult animals. However, in late cultures, release of proteoglycans was reduced in the presence of L-NMA. The proteolytic activity in conditioned medium of these cultures (measured as caseinolytic activity) was enhanced by L-NMA; however, this inhibitor did not affect the rates of synthesis of proteoglycans. Although NO is widely assumed to be a mediator of cartilage catabolism, our data suggest that it may instead have an acute protective effect. Whether this effect is maintained chronically is less clear.

Original languageEnglish (US)
Pages (from-to)1213-1220
Number of pages8
JournalJournal of Immunology
Volume156
Issue number3
StatePublished - Feb 1 1996
Externally publishedYes

Fingerprint

Organ Culture Techniques
Articular Cartilage
Proteoglycans
Nitric Oxide
Chondrocytes
Cartilage
Conditioned Culture Medium
Metabolic Networks and Pathways
Interleukin-1
Nitric Oxide Synthase
Arginine
Joints

ASJC Scopus subject areas

  • Immunology

Cite this

Stefanovic-Racic, M., Morales, T. I., Taskiran, D., McIntyre, L. A., & Evans, C. H. (1996). The role of nitric oxide in proteoglycan turnover by bovine articular cartilage organ cultures. Journal of Immunology, 156(3), 1213-1220.

The role of nitric oxide in proteoglycan turnover by bovine articular cartilage organ cultures. / Stefanovic-Racic, M.; Morales, T. I.; Taskiran, D.; McIntyre, L. A.; Evans, Christopher H.

In: Journal of Immunology, Vol. 156, No. 3, 01.02.1996, p. 1213-1220.

Research output: Contribution to journalArticle

Stefanovic-Racic, M, Morales, TI, Taskiran, D, McIntyre, LA & Evans, CH 1996, 'The role of nitric oxide in proteoglycan turnover by bovine articular cartilage organ cultures', Journal of Immunology, vol. 156, no. 3, pp. 1213-1220.
Stefanovic-Racic M, Morales TI, Taskiran D, McIntyre LA, Evans CH. The role of nitric oxide in proteoglycan turnover by bovine articular cartilage organ cultures. Journal of Immunology. 1996 Feb 1;156(3):1213-1220.
Stefanovic-Racic, M. ; Morales, T. I. ; Taskiran, D. ; McIntyre, L. A. ; Evans, Christopher H. / The role of nitric oxide in proteoglycan turnover by bovine articular cartilage organ cultures. In: Journal of Immunology. 1996 ; Vol. 156, No. 3. pp. 1213-1220.
@article{76f17076bc8c4d7ebb0065d8b824a3f4,
title = "The role of nitric oxide in proteoglycan turnover by bovine articular cartilage organ cultures",
abstract = "Monolayer cultures of articular chondrocytes synthesize large amounts of nitric oxide (NO) following exposure to IL-1. The latter has antianabolic and procatabolic activities on these cells, but little is known about the role, if any, of NO in the integrated metabolic pathways of the chondrocyte. In the present study, the role of endogenously produced NO in both the synthesis and degradation of proteoglycans was investigated for the first time. Bovine articular cartilage slices exposed to 20 U/ml human rIL-1β (hrIL-1β) synthesized large amounts of NO for 1 to 2 days, after which production fell to a steady state level ~20{\%} of the peak value for the remainder of the 14- day incubation. The NO synthase inhibitor, N-monomethyl L-arginine (L-NMA, 1 mM), blocked NO production and enhanced the acute catabolic effects of hrIL- 1β in cartilage derived from both calves and adult animals. However, in late cultures, release of proteoglycans was reduced in the presence of L-NMA. The proteolytic activity in conditioned medium of these cultures (measured as caseinolytic activity) was enhanced by L-NMA; however, this inhibitor did not affect the rates of synthesis of proteoglycans. Although NO is widely assumed to be a mediator of cartilage catabolism, our data suggest that it may instead have an acute protective effect. Whether this effect is maintained chronically is less clear.",
author = "M. Stefanovic-Racic and Morales, {T. I.} and D. Taskiran and McIntyre, {L. A.} and Evans, {Christopher H}",
year = "1996",
month = "2",
day = "1",
language = "English (US)",
volume = "156",
pages = "1213--1220",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "3",

}

TY - JOUR

T1 - The role of nitric oxide in proteoglycan turnover by bovine articular cartilage organ cultures

AU - Stefanovic-Racic, M.

AU - Morales, T. I.

AU - Taskiran, D.

AU - McIntyre, L. A.

AU - Evans, Christopher H

PY - 1996/2/1

Y1 - 1996/2/1

N2 - Monolayer cultures of articular chondrocytes synthesize large amounts of nitric oxide (NO) following exposure to IL-1. The latter has antianabolic and procatabolic activities on these cells, but little is known about the role, if any, of NO in the integrated metabolic pathways of the chondrocyte. In the present study, the role of endogenously produced NO in both the synthesis and degradation of proteoglycans was investigated for the first time. Bovine articular cartilage slices exposed to 20 U/ml human rIL-1β (hrIL-1β) synthesized large amounts of NO for 1 to 2 days, after which production fell to a steady state level ~20% of the peak value for the remainder of the 14- day incubation. The NO synthase inhibitor, N-monomethyl L-arginine (L-NMA, 1 mM), blocked NO production and enhanced the acute catabolic effects of hrIL- 1β in cartilage derived from both calves and adult animals. However, in late cultures, release of proteoglycans was reduced in the presence of L-NMA. The proteolytic activity in conditioned medium of these cultures (measured as caseinolytic activity) was enhanced by L-NMA; however, this inhibitor did not affect the rates of synthesis of proteoglycans. Although NO is widely assumed to be a mediator of cartilage catabolism, our data suggest that it may instead have an acute protective effect. Whether this effect is maintained chronically is less clear.

AB - Monolayer cultures of articular chondrocytes synthesize large amounts of nitric oxide (NO) following exposure to IL-1. The latter has antianabolic and procatabolic activities on these cells, but little is known about the role, if any, of NO in the integrated metabolic pathways of the chondrocyte. In the present study, the role of endogenously produced NO in both the synthesis and degradation of proteoglycans was investigated for the first time. Bovine articular cartilage slices exposed to 20 U/ml human rIL-1β (hrIL-1β) synthesized large amounts of NO for 1 to 2 days, after which production fell to a steady state level ~20% of the peak value for the remainder of the 14- day incubation. The NO synthase inhibitor, N-monomethyl L-arginine (L-NMA, 1 mM), blocked NO production and enhanced the acute catabolic effects of hrIL- 1β in cartilage derived from both calves and adult animals. However, in late cultures, release of proteoglycans was reduced in the presence of L-NMA. The proteolytic activity in conditioned medium of these cultures (measured as caseinolytic activity) was enhanced by L-NMA; however, this inhibitor did not affect the rates of synthesis of proteoglycans. Although NO is widely assumed to be a mediator of cartilage catabolism, our data suggest that it may instead have an acute protective effect. Whether this effect is maintained chronically is less clear.

UR - http://www.scopus.com/inward/record.url?scp=0030025492&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030025492&partnerID=8YFLogxK

M3 - Article

C2 - 8558000

AN - SCOPUS:0030025492

VL - 156

SP - 1213

EP - 1220

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 3

ER -