Osteoclast resorption-stimulating activity is associated with the osteoblast cell surface and/or the extracellular...

Osteoblasts mediate much of the hormonal responsiveness of osteoclasts. We and others have found that one mechanism through which this regulation is effected is by release of osteoclast resorption-stimulating activity (ORSA) into culture supernatants. However, although hormonal responsiveness is regularly observed in co-cultures, ORSA is not always detectable in conditioned media. We show here that one explanation for this finding is that ORSA may be retained by heparin-like glycosaminoglycans (GAGs) of the cell surface or extracellular matrix of osteoblasts. We found that protease-sensitive ORSA could be extracted from monolayers of the osteoblastic cell line UMR 106 with 2M NaCl or collagenase. Production of this activity was increased in response to 1,25(OH)2D3. The presence of the GAG heparin was required to reveal ORSA. Immobilisation of ORSA by GAGs may assist osteoblastic cells in the regulation of the complex patterns of osteoclastic activity observed during skeletal morphogenesis and restructuring.