Expression of opioid receptors in osteoblast-like MG-63 cells, and effectsof different opioid agonists on alkaline phosphatase and osteocalcin secretion by these cells

We have previously shown that several stressful situations associated with tissue injury determine a decrease in serum osteocalcin concentration. Sinc e reduced osteocalcin production is a marker of decreased osteoblastic acti vity, this finding could be related to the pathogenesis of osteoporosis sec ondary to some diseases. Endogenous opioids are involved in stress response . Proenkephalin-derived peptides have been shown to inhibit alkaline phosph atase activity, another marker of bone formation, in the murine cell line R OS-17/2.8. On the other hand, serum osteocalcin has been reported as being low in heroin abusers. We have therefore thought it of interest to study th e presence of opioid receptors in the human osteoblast-like cell line MG-63 , and to evaluate the effects of different opioid agonists on the secretion of alkaline phosphatase and osteocalcin by these cells. The presence of op ioid receptors was studied by means of RT-PCR and immunohistochemistry. RT- PCR studies suggested the presence of specific mRNA for the three types of receptors, and immunohistochemistry clearly showed their occurrence. Osteoc alcin synthesis was significantly inhibited by high concentrations of the m u agonists morphine and (D-Ala(2),N-MePhe(4),Gly(5)-ol)-enkephalin although no changes were seen with the delta agonist (DAla(2),D-leu(5))-enkephalin. Morphine-induced osteocalcin inhibition was abolished when osteoblastic ce lls were incubated simultaneously with naloxone, whereas it was potentiated when cells were preincubated with naloxone. None of the opioid agonists mo dified the secretion of alkaline phosphatase. In conclusion, human osteobla stlike cells MG-63 express the three types of opioid receptors. Endogenous opioids may be involved in the reduction of osteocalcin observed in stressf ul situations associated with tissue injury. Copyright (C) 2000 S. Karger A G, Basel.