Osteogenic protein 1 stimulates cells-associated matrix assembly by normal human articular chondrocytes: up-regulation of hyaluronan synthase, CD44, and aggrecan.
OBJECTIVE
To determine the effects of osteogenic protein 1 (OP-1) on hyaluronan (HA), CD44, and aggrecan biosynthesis as well as the contribution of these molecules in promoting matrix assembly by human articular chondrocytes.


METHODS
Normal human chondrocytes were cultured with or without OP-1 treatment. Changes in the relative expression of messenger RNA (mRNA) for HA synthases 2 and 3 (HAS-2 and HAS-3), CD44, and aggrecan were determined by competitive quantitative reverse transcriptase-polymerase chain reaction. Accumulation of HA was characterized by indirect staining, CD44 by flow cytometry, and aggrecan biosynthesis by 35SO4 incorporation.


RESULTS
OP-1 stimulated the expression of HAS-2, CD44, and aggrecan mRNA in a time-dependent manner, resulting in increased expression of HA, CD44, and aggrecan. Prominent increases in HA-rich cell-associated matrices were also observed.


CONCLUSIONS
OP-1 stimulates not only the synthesis of matrix macromolecules such as aggrecan, but also the synthesis of other molecules required for matrix retention, namely, HA and CD44.
Nishida
Y
Y
Rush Medical College, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612, USA.
Knudson
C B
CB
Eger
W
W
Kuettner
K E
KE
Knudson
W
W
D053674:Aggrecans; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D002358:Cartilage, Articular / Q000166:cytology / Q000378:metabolism; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005434:Flow Cytometry; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000276:immunology; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics; D016695:Glycosyltransferases; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics*; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000096:biosynthesis; D007700:Kinetics; D037181:Lectins, C-Type; D008565:Membrane Proteins / Q000235:genetics; D016133:Polymerase Chain Reaction; D011509:Proteoglycans / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D014166:Transferases; D016212:Transforming Growth Factor beta; D029867:Xenopus Proteins
D053674:Aggrecans; C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D016326:Extracellular Matrix Proteins; D018960:Hyaluronan Receptors; D037181:Lectins, C-Type; D008565:Membrane Proteins; D011509:Proteoglycans; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D029867:Xenopus Proteins; C525822:bmp7.1 protein, Xenopus; D006820:Hyaluronic Acid; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D014166:Transferases; D016695:Glycosyltransferases; D014453:Glucuronosyltransferase; C056944:HAS1 protein, Xenopus; D000076002:Hyaluronan Synthases