Mode of action of cortisol on bone resorption in fetal rat fibulae cultured in vitro

Several concentrations of cortisol (10 ‐8 to 10 ‐6 M) were tested for their ability to inhibit the spontaneous or parathyroid extract‐induced (PTE) bone resorption in organ cultures of 19‐day‐old fetal rat fibulae. The criteria used for the assessment of bone resorption were: the release of 45 Ca from pre‐labeled bone rudiments into the culture medium, the dry weight and the number of osteoclasts per bone. At a dose of 10 ‐6 M, cortisol diminished significantly the release of 45 Ca from fetal fibulae. This inhibition was accompanied by an increase in bone dry weight and by reduced numbers of osteoclasts. PTE, alone, caused extensive bone resorption with numerous osteoclasts and enhanced 45 Ca release, without weight gain. This resorptive action of PTE was partially suppressed by cortisol at a dose of 10 ‐6 M. Lower concentrations were ineffective. Radioautographic studies with 3 H‐thymidine revealed that cortisol restricts the recruitment of osteoclasts from osteoprogenitor cells, without decreasing the potential of precursor cells to form osteoblasts. PTE, however, stimulates the proliferation of progenitor cells and favors their differentiation towards osteoclasts. This effect can be suppressed by cortisol. It is concluded that cortisol inhibits bone resorption in vitro by limiting the ability of precursor cells to form osteoclasts. Moreover, our study shows that, in fetal rat bones cultured in vitro, osteoclasts arise from locally proliferating mononucleated precursor cells.