Abstract
The present study investigated effects of inhibiting the synthesis of prostaglandins (PGs) on cyclic AMP concentrations and chondrogenesis in cultured chick limb mesenchyme. Indomethacin produced concentration-dependent inhibition of both PGE2 synthesis and chondrogenesis over a concentration range of 50--200 μM. Half maximal inhibition of PGE2 was achieved with 50 μM concentrations of the drug which also produced visibly reduced amounts of cartilage matrix in cell cultures as evaluated by Alcian green staining on day 6 of culture. The inhibitory effects of indomethacin on chondrogenesis were largely reversed by addition of 1 mM dibutyryl cAMP, indicating that cells could still respond to cyclic AMP stimulation. Endogenous levels of cyclic AMP, which increased by 6 fold during the six days of culture in control cells, did not increase significantly from dissociated cells at the time of plating (day 0) in indomethacin-treated cultures. The results indicate that inhibition of the prechondrogenic rise in PGE2 concentrations in limb mesenchyme prevents the increase in cyclic AMP levels which occur during this same period resulting in inhibition of chondrogenesis. The data provide further support for the hypothesis that PGE2, through its effects on the adenylate cyclase-cAMP system, plays an important role in the differentiation of cartilage.
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Biddulph, D.M., Dozier, M.M. & Capehart, A.A. Inhibition of prostaglandin synthesis reduces cyclic AMP levels and inhibits chondrogenesis in cultured chick limb mesenchyme. Methods Cell Sci 22, 9–16 (2000). https://doi.org/10.1023/A:1009824106368
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DOI: https://doi.org/10.1023/A:1009824106368