Journal
AMERICAN JOURNAL OF PATHOLOGY
Volume 169, Issue 2, Pages 491-502Publisher
ELSEVIER SCIENCE INC
DOI: 10.2353/ajpath.2006.050738
Keywords
-
Categories
Ask authors/readers for more resources
Osteoarthritic (OA) chondrocytes are metabolically active, displaying increased synthesis of type H collagen. Here, we show by immunohistochemistry and polymerase chain reaction that in comparison with healthy cartilage, OA articular chondrocytes; exhibit increased in vivo synthesis of collagen prolyl-4-hydroxylase type II, a pivotal enzyme in collagen triple helix formation. Exposure of primary human articular chondrocytes to 1% oxygen enhanced accumulation of native type H collagen and stabilized hypoxia-inducible factor-la (HEF-1 alpha). This effect was abolished by addition of the HIF-1 inhibitor 2-methoxyestradiol. Real-time polymerase chain reaction analyses of mRNAs from these cultures revealed increased transcript levels of both alpha-subunits of prolyl-4-hydroxylase (P4HA1, similar to 2-fold; P4HA2, similar to 2.3-fold) and of classical HIF-1 target genes (glucosetransporter-1, similar to 2.1-fold; phosphoglyceratekinase-1, similar to 2.2-fold). Treatment of hypoxic chondrocytes; with 2-methoxyestradiol reduced transcriptional activity of HIT-1 and synthesis of a(H), and to a lesser extent alpha(I), subunits of collagen prolyl-4-hydroxylases. mRNA levels of type H collagen (Col2A1) and the beta-subunit (P4HB) of prolyl-4-hydroxylase, however, displayed only modest changes at 1% oxygen. From these results and our in vivo data, we inferred that besides increased Col2A1 mRNA expression by OA chondrocytes, accelerated posttranslational modification processes might contribute to the increased synthesis and accumulation of type H collagen during OA and experimental hypoxia.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available