Generation of nitric oxide by lapine meniscal cells and its effect on matrix metabolism: Stimulation of collagen production by arginine

M. Cao, M. Stefanovic-Racic, H. I. Georgescu, L. A. Miller, C. H. Evans

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

Slices of lapine meniscus produced large amounts of nitric oxide after stimulation with interleukin-1, tumor necrosis factor α, or a mixture of lapine synovial cytokines known as chondrocyte-activating factors. Monolayer cultures of meniscal cells produced from the proteolysis of meniscal tissue contained a mixed population of chondrocytic and fibroblastic cells. These cultures also produced large amounts of nitric oxide in response to cytokines. Monolayer cultures of meniscal cells produced by the explant method, in contrast, were uniformly fibroblastic and did not produce nitric oxide in response to cytokines. We conclude that menisci contain two populations of cells, one fibroblastic and the other chondrocytic. The chondrocytic cells are responsible for generating most of the nitric oxide in response to cytokines. Endogenously generated nitric oxide suppressed the synthesis of collagen and proteoglycan by menisci but protected proteoglycan from the catabolic effects of interleukin-1. The inhibitory effect of nitric oxide on collagen synthesis occurred without greatly altering the abundance of mRNAs encoding the various collagen α chains. During further investigation, arginine was unexpectedly found to stimulate the synthesis of collagen and, to a lesser degree, of noncollagenous proteins but not of proteoglycans. Fragments of meniscus, but not meniscal cells in monolayer culture, increased their production of matrix metalloproteinases, lactate, and, especially, prostaglandin E2 in response to interleukin-1. Inhibition of nitric oxide production with N(G))-monomethyl-L-arginine enhanced production of matrix metalloproteinases but had little effect on the synthesis of lactate or prostaglandin E2.

Original languageEnglish (US)
Pages (from-to)104-111
Number of pages8
JournalJournal of Orthopaedic Research
Volume16
Issue number1
DOIs
StatePublished - Jan 1 1998

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

Fingerprint Dive into the research topics of 'Generation of nitric oxide by lapine meniscal cells and its effect on matrix metabolism: Stimulation of collagen production by arginine'. Together they form a unique fingerprint.

  • Cite this