CALCITONIN RESPONSIVENESS AND RECEPTOR EXPRESSION IN PORCINE AND MURINE OSTEOCLASTS - A COMPARATIVE-STUDY

The presence of the calcitonin (CT) receptor is a distinguishing chara cteristic of osteoclasts; however, species variability exists with res pect to functional responsiveness to CT. In the present study, CT resp onsiveness and temporal expression of the CT receptor in differentiati ng cultures of porcine osteoclasts was examined and compared to murine osteoclasts. In vitro porcine osteoclast differentiation was evaluate d using bone marrow cultures from neonatal pigs, Murine osteoclast dif ferentiation was studied using cocultures of murine bone marrow and BA LC cells, a calvarial-derived cell line. In the presence of 1,25 (OH)( 2)D-3, a time-dependent increase in osteoclast differentiation was obs erved in porcine and murine cultures, Salmon CT (sCT) and porcine CT ( pCT) inhibited 1,25 (OH)(2)D-3-stimulated porcine osteoclast different iation at 10(-8) and 10(-7) mol/L (60% with 10(-7) mol/L sCT and 85% i nhibition with 10(-7) mol/L pCT). Treatment of murine cocultures with sCT (10(-17)-10(-7) mol/L) resulted in a concentration-dependent decre ase in osteoclast differentiation with a maximal inhibition of 70%. Os teoclast differentiation was inhibited in a concentration-dependent ma nner by recombinant human transforming growth factor-beta1 (rhTGF-beta 1) in both species, The effects of CT on resorption lacunae formation were determined by culturing in vitro generated porcine or murine ost eoclasts on bovine cortical bone slices for 18 h in the presence or ab sence of CT, With both porcine and murine osteoclasts, a concentration -dependent decrease in resorption lacunae formation was observed betwe en 10(-13) and 10(-7) mol/L sCT with the highest concentrations comple tely abolishing resorption, However, pCT only inhibited porcine osteoc lastic resorption at 10(-7) mol/L, CT receptor messenger ribonucleic a cid (mRNA) expression was determined at different time points during i n vitro osteoclast differentiation, In porcine cultures, expression of CT receptor mRNA correlated with the presence of osteoclasts. In muri ne cocultures, mRNA for the CT receptor was observed at each time poin t examined and was independent of the presence of multinucleated osteo clasts. Thus, porcine and murine differentiating osteoclast cultures e xpress CT receptor mRNA; however, receptor expression correlates with osteoclast formation only in the porcine cultures. In summary, porcine and murine osteoclasts express CT receptor mRNA and functional respon siveness to CT. These findings suggest that the effects of sCT on oste oclast resorption are similar in murine and porcine cells, but that sC T is a less potent inhibitor of porcine than murine osteoclast differe ntiation. (Bone 23:233-240; 1998) (C) 1998 by Elsevier Science Inc. Al l rights reserved.