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Inhibitory effect of auranofin (I) and chloroquine (II) on bone degradation induced by the interleukin 1-like (IL-1-like) factor released from rheumatoid synovial tissue (RAST) in vitro

Conference · · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)
OSTI ID:5506717
; ; ; ; ;

RAST, maintained in organ culture, releases two distinct types of bone resorptive factors and one co-resorptive factor. The first is prostaglandin E/sub 2/ (PGE/sub 2/), while the second is a protein with properties of IL-1. The co-resorptive factor collagenase, cannot induce bone resorption by itself, but augments the bone resorptive activity initiated by either PGE/sub 2/ or the IL-l-like factor. Bone resorptive activity was assessed by measuring the release of /sup 45/Ca from prelabelled rat fetal bones. We investigated the effects of five non-steroidal anti-inflammatory drugs (NSAIDs) and two disease-modifying anti-rheumatic drugs (DMARDs), (I) and (II), on bone degradation mediated by the IL-l-like factor. None of the NSAIDs tested inhibited bone degradation at 5 x 10/sup -5/ M. On the other hand, both (I) and (II) inhibited bone degradation 60 to 100% at 1 x 10/sup -6/ M and 8 x 10/sup -6/ M respectively. They can inhibit the action of IL-l-like factor on bone at therapeutically attainable concentrations. Additionally, both (I) and (II) block the release of collagenase from the organ culture of RAST with IC/sub 50/s of 5 x 10/sup -6/ M. This unique ability to inhibit collagenase release may contribute to their effectiveness is preventing bone loss in this test model.

Research Organization:
Syntex Research, Palo Alto, CA
OSTI ID:
5506717
Report Number(s):
CONF-8604222-
Journal Information:
Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Vol. 45:3; ISSN FEPRA
Country of Publication:
United States
Language:
English

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Related Subjects

550901* -- Pathology-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALKALINE EARTH ISOTOPES
ANTIPYRETICS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL EFFECTS
BODY
CALCIUM 45
CALCIUM ISOTOPES
CENTRAL NERVOUS SYSTEM DEPRESSANTS
CHEMICAL REACTIONS
DAYS LIVING RADIOISOTOPES
DECOMPOSITION
DISEASES
DRUGS
ENZYMES
EVEN-ODD NUCLEI
GROWTH FACTORS
HYDROLASES
INTERMEDIATE MASS NUCLEI
ISOTOPE APPLICATIONS
ISOTOPES
LYMPHOKINES
MITOGENS
NUCLEI
ORGANIC COMPOUNDS
ORGANS
PEPTIDE HYDROLASES
PROSTAGLANDINS
PROTEINS
RADIOISOTOPES
SKELETAL DISEASES
SKELETON
TISSUE CULTURES
TRACER TECHNIQUES