Modulation of Superficial Zone Protein/Lubricin/PRG4 by Kartogenin and Transforming Growth Factor-β1 in Surface Zone Chondrocytes in Bovine Articular Cartilage.
OBJECTIVE
Superficial zone protein (SZP)/lubricin/PRG4 functions as a boundary lubricant in articular cartilage to decrease friction and wear. As articular cartilage lubrication is critical for normal joint function, the accumulation of SZP at the surface of cartilage is important for joint homeostasis. Recently, a heterocyclic compound called kartogenin (KGN) was found to induce chondrogenic differentiation and enhance mRNA expression of lubricin. The objective of this study was to determine whether KGN can stimulate synthesis of SZP in superficial zone, articular chondrocytes.


METHODS
We investigated the effects of KGN and transforming growth factor-β1 (TGF-β1) on articular cartilage and synovium of the bovine knee joint by evaluating SZP secretion by enzyme-linked immunosorbent assay analysis. Monolayer, micromass, and explant cultures of articular cartilage, and monolayer culture of synoviocytes, were treated with KGN. SZP accumulation in the medium was evaluated and mRNA expression was measured through quantitative polymerase chain reaction.


RESULTS
TGF-β1 stimulated SZP secretion by superficial zone chondrocytes in monolayer, explant, and micromass cultures as expected. In addition, SZP secretion was inhibited by IL-1β in explant cultures, and enhanced by TGF-β1 in synoviocyte monolayer cultures. Although KGN elicited a 1.2-fold increase in SZP mRNA expression in combination with TGF-β1, KGN neither stimulated any significant increases in SZP synthesis nor prevented catabolic decreases in SZP production from IL-1β.


CONCLUSIONS
These data suggest that the chondrogenic effects of KGN depend on cellular phenotype and differentiation status, as KGN did not alter SZP synthesis in differentiated, superficial zone articular chondrocytes.
Department of Orthopaedic Surgery, Lawrence Ellison Center for Tissue Regeneration and Repair, School of Medicine, University of California, Davis, Sacramento, CA, USA.
Kazumasa
K
Miyatake
Department of Orthopaedic Surgery, Lawrence Ellison Center for Tissue Regeneration and Repair, School of Medicine, University of California, Davis, Sacramento, CA, USA.
Kenjiro
K
Iwasa
Department of Orthopaedic Surgery, Lawrence Ellison Center for Tissue Regeneration and Repair, School of Medicine, University of California, Davis, Sacramento, CA, USA.
Sean M
SM
McNary
Department of Orthopaedic Surgery, Lawrence Ellison Center for Tissue Regeneration and Repair, School of Medicine, University of California, Davis, Sacramento, CA, USA.
Gordon
G
Peng
Department of Orthopaedic Surgery, Lawrence Ellison Center for Tissue Regeneration and Repair, School of Medicine, University of California, Davis, Sacramento, CA, USA.
A Hari
AH
Reddi
articular cartilage; kartogenin; lubricin; superficial zone protein (SZP); transforming growth factor-β1 (TGF-β1)
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