Synthesis of collagen by chondrocytes in suspension culture: Modulation by calcium, 3′:5′-cyclic AMP, and prostaglandins

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Abstract
Rabbit articular chondrocytes synthesize type II collagen [3α 1 (II)] in vivo and type I collagen [2α 1 (I)·α 2 ] in monolayer cultures. In suspension culture the nature of phenotype depends on extracellular Ca 2+ . The relationship of Ca 2+ and 3′:5′-cyclic AMP (cAMP) in regulation of collagen synthesis has been investigated. In suspension culture, cAMP levels of chondrocytes increase by 2- to 3-fold and then reach basal values regardless of the presence or absence of extracellular Ca 2+ . The cells, however, synthesize primarily type II collagen in the absence of CaCl 2 in the medium and type I collagen in medium containing 1.8 mM CaCl 2 . If CaCl 2 is added when intracellular cAMP levels are low, the phenotype is type I collagen. These observations minimize the role of cAMP as a second messenger in the chondrocyte culture system. Increasing endogenous cAMP with a phosphodiesterase inhibitor or adding exogenous dibutyryl-cAMP leads the cells to synthesize type I collagen, although this effect is significantly less pronounced if the medium contains ethylene glycol bis(β-aminoethyl ether)- N,N ′-tetraacetic acid (EGTA). Increased concentrations of cAMP may mobilize the intracellular calcium pools and activate the cells to switch their phenotypic expression. Prostaglandins E 2 and F 2 α, thought to be involved in rheumatoid arthritis and bone resorption, have no significant effect on cAMP content of chondrocytes and alter their collagen phenotype to a small extent.