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MR Vol.13 No.1 indexに戻る
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MODERN RHEUMATOLOGY
Vol.13 No.1 |
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Extracellular matrix recovery by human articular
chondrocytes after treatment with hyaluronan hexasaccharides or Streptomyces
hyaluronidase |
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| Y. Nishida1, C. B. Knudson2, W. Knudson2 |
(1)Department of Orthopaedic Surgery, Nagoya
University School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-8550,
Japan
(2)
Department of Biochemistry, Rush Medical College, Rush-Presbyterian-St.Luke's
Medical Center, Chicago, IL, USA |
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| Abstract |
| Abstract The treatment of human articular
chondrocytes with Streptomyces hyaluronidase (St-HA'ase) or hyaluronan
hexasaccharides (HA6) provides two approaches to the selective
depletion of specific components of the extracellular matrix, and
an opportunity to follow the reparative responses initiated by
these changes. In this study, changes in the relative expression
of messenger RNA for hyaluronan synthase-2, CD44, and aggrecan
were determined by competitive, quantitative reverse transcriptase-polymerase
chain reaction. Changes in the size of the cell-associated matrix
surrounding live chondrocytes were analyzed by the particle exclusion
assay, and hyaluronan accumulation was characterized using a biotin-labeled
hyaluronan-specific binding protein. Both Streptomyces hyaluronidase
as well as hyaluronan hexasaccharide treatment of chondrocytes
resulted in an approximately 2-fold increase in hyaluronan synthase-2
mRNA copy numbers, together with a 1.8-fold increase in the mRNA
copy number for the proteoglycan aggrecan. However, although matrix
biosynthesis was enhanced, the chondrocytes failed to retain these
components. Both treatments resulted in a diminished accumulation
of extracellular hyaluronan as well as a loss of the chondrocyte
proteoglycan-rich cell-associated matrix. Thus, this model is similar
to the early stages of osteoarthritis. Upon removal of the Streptomyces
hyaluronidase or hyaluronan hexasaccharides, the normal, healthy,
adult human chondrocytes used in this study regained their capacity
to retain extracellular hyaluronan and to reassemble and retain
a cell-associated matrix. This stimulation of hyaluronan synthase-2
(HAS-2) and aggrecan mRNA expression, and the subsequent capacity
to retain the newly synthesized extracellular matrix, illustrate
the events which are necessary for adult human articular chondrocytes
to undergo effective repair. |
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| Key words |
| Key words Articular chondrocytes ・ Extracellular
matrix ・ Hyaluronan hexasaccharides (HA 6 ) ・ Hyaluronan synthase
(HAS) ・ Streptomyces
hyaluronidase ( St -HA′ase) |
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