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2016 ; 7
(4
): 388-97
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Modulation of Superficial Zone Protein/Lubricin/PRG4 by Kartogenin and
Transforming Growth Factor-?1 in Surface Zone Chondrocytes in Bovine Articular
Cartilage
#MMPMID27688846
Miyatake K
; Iwasa K
; McNary SM
; Peng G
; Reddi AH
Cartilage
2016[Oct]; 7
(4
): 388-97
PMID27688846
show ga
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. DESIGN: We investigated the effects of KGN and
transforming growth factor-?1 (TGF-?1) 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-?1 stimulated SZP secretion
by superficial zone chondrocytes in monolayer, explant, and micromass cultures as
expected. In addition, SZP secretion was inhibited by IL-1? in explant cultures,
and enhanced by TGF-?1 in synoviocyte monolayer cultures. Although KGN elicited a
1.2-fold increase in SZP mRNA expression in combination with TGF-?1, KGN neither
stimulated any significant increases in SZP synthesis nor prevented catabolic
decreases in SZP production from IL-1?. 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.