The in vitro effect of indomethacin on basal bone resorption, on prostaglandin production and on the response to added prostaglandins

Abstract

Mouse calvaria were maintained in organ culture without serum additives. Basal active resorption, as measured by 45Ca and hydroxyproline release, was significantly inhibited to 74% control levels by indomethacin (1.4 × 10 −7 M). Prostaglandin F and prostaglandin E 2 production, determined by radioimmunoassay, were both significantly lowered by this concentration of indomethacin. DNA, protein and hydroxyproline synthesis, as indices of cell toxicity, were unaffected by low concentrations of indomethacin, while concentrations of 1.4 × 10 −6M inhibited protein synthesis (p<0.005). In the presence of indomethacin (1.4 × 10 −7M) both PGE 2 and PGF 2α stimulated resorption in a dose-dependent manner, with PGE 2 being the more potent. Neither prostaglandin affected hydroxyproline synthesis at low concentrations, but PGE 2 had a marked inhibitory action at a higher concentration (10 −6M). In combination, the effects of PGE 2 and PGF 2α showed no evidence of synergism or any antagonistic action. The study shows that in vitro calcium and hydroxyproline resorption in the unstimulated mouse calvaria are inhibited by indomethacin at concentrations measured in serum during human therapy. The decreased PGF and PGE 2 production associated with this decreased bone resorption in the presence of non-toxic concentrations of indomethacin would suggest a role for these prostaglandins in maintaining the basal resorption of cultured bone.