EFFECTS OF ELECTROMAGNETIC STIMULATION ON THE FUNCTIONAL RESPONSIVENESS OF ISOLATED RAT OSTEOCLASTS

We report the effects of pulsed electromagnetic fields (PEMFs) on the responsiveness of osteoclasts to cellular, hormonal, and ionic signals . Osteoclasts isolated from neonatal rat long bones were dispersed ont o either slices of devitalised cortical bone (for the measurement of r esorptive activity) or glass coverslips (for the determination of the cytosolic free Ca2+ concentration, [Ca2+]). Osteoclasts were also cocu ltured on bone with osteoblastlike, UMR-106 cells. Bone resorption was quantitated by scanning electron microscopy and computer-assisted mor phometry. PEMF application to osteoblast-osleoclast cocultures for 18 hr resulted in a twofold stimulation of bone resorption. In contrast, resorption by isolated osteoclasts remained unchanged in the presence of PEMFs, suggesting that osteoblasts were necessary for the PEMF-indu ced resorption simulation seen in osteoblast-osteoclast cocultures. Fu rthermore, the potent inhibitory action of the hormone calcitonin on b one resorption was unaffected by PEMF application. However, PEMFs comp letely reversed another quite distinct action of calcitonin on the ost eoclast: its potent inhibitory effect on the activation of the divalen t cation-sensing (or Ca2+) receptor. For these experiments, we made fu ra 2-based measurements of cytosolic [Ca2+] in single osteoclasts in r esponse to the application of a known Ca2+ receptor agonist, Ni2+. We first confirmed that activation of the osteoclast Ca2+ receptor by Ni2 + (5 mM) resulted in a characteristic monophasic elevation of cytosoli c [Ca2+]. As shown previously, this response was attenuated strongly b y calcitonin at concentrations between 0.03 and 3 nM but remained inta ct in response to PEMFs. PEMF application, however, prevented the inhi bitory effect of calcitonin on Ni2+-induced cytosolic Ca2+ elevation. This suggested that the fields disrupted the interaction between the c alcitonin and Ca2+ receptor systems. In conclusion, we have shown that electromagnetic fields stimulate bone resorption through an action on the osteoblast and, by abolishing the inhibitory effects of calcitoni n, also restore the responsiveness of osteoclasts to divalent cations. J. Cell. Physiol. 176:537-544, 1998. (C) 1998 Wilev-Liss, Inc.