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Journal of Histochemistry and Cytochemistry, Vol. 48, 239-250, February 2000, Copyright © 2000, The Histochemical Society, Inc.
Human Articular Chondrocytes Express Osteogenic Protein-1
Susan Chubinskayaa,
Charis Merrihewa,
Gabriella Cs-Szaboa,b,
Juergen Mollenhauera,c,
John McCartneya,c,
David C. Ruegerd, and
Klaus E. Kuettnera,b
a Departments of Biochemistry, Rush Medical College, Rush-PresbyterianSt. Luke's Medical Center, Chicago, Illinois
b Orthopedic Surgery, Rush Medical College, Rush-PresbyterianSt. Luke's Medical Center, Chicago, Illinois
c Creative BioMolecules, Hopkinton, Massachusetts
d Stryker Biotech, Hopkinton, Massachusetts
Correspondence to:
Susan Chubinskaya, Dept. of Biochemistry, Rush Medical College at RushPresbyterianSt. Luke's Medical Center, 1653 W. Congress Parkway, Chicago, IL 60612.
This study demonstrates for the first time that human articular chondrocytes express osteogenic protein-1 (OP-1). OP-1 was originally purified from bone matrix and was shown to induce cartilage and bone formation. Both OP-1 protein and message were present in human normal and osteoarthritic (OA) cartilages. OP-1 mRNA was upregulated in OA cartilage compared with normal adult tissues. However, the level of mature OP-1 protein in the same OA tissues was downregulated, whereas the pro-OP-1 remained high. Moreover, these two forms of OP-1 were localized in an inverted manner. Mature OP-1 was primarily detected in the superficial layer, whereas the pro-form was mostly in the deep layer of cartilage. The presence of pro- and mature OP-1 in extracts of normal and OA cartilages was confirmed by Western blotting. These findings imply that articular chondrocytes continue to express and synthesize OP-1 throughout adulthood. The observed patterns of the distribution of pro- and mature OP-1 also suggest differences in the processing of this molecule by normal and OA chondrocytes and by the cells in the superficial and deep layers. Distinct distribution of OP-1 and its potential activation in deep zones and regions of cloning in OA cartilages may provide clues to the potential involvement of endogenous OP-1 in repair mechanisms. (J Histochem Cytochem 48:239250, 2000)
Key Words:
osteogenic protein-1, human articular cartilage, in situ hybridization, comparative RT-PCR, immunohistochemistry, Western blotting

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