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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. Knudson 2 |
(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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