PTH-MEDIATED OSTEOBLAST RETRACTION - POSSIBLE PARTICIPATION OF THE CALPAIN PATHWAY

Parathyroid hormone (PTH)-induced osteoblast retraction may play a piv otal role in bone resorption by providing osteoclasts direct access to mineralized bone surface. We have been working on the hypothesis that the calpains participate in this retractile response through a calciu m-dependent process, We have first demonstrated the presence of calpai n activities in MC3T3-E1 osteoblastic cells and that these activities can be stimulated by PTH, Second, we have demonstrated that the PTH-in duced osteoblast retraction is dramatically attenuated by two differen t cysteine protease inhibitors. Finally, initial immunofluorescent cyt ochemical studies suggest that this PTH-induced osteoblastic retractio n is mediated through a calpain-dependent, proteolytic modification of the cytoskeletal organization.