Osteoblasts release osteoclasts from calcitonin-induced quiescence

Abstract

There is an increasing body of indirect evidence that suggests that the localization and activity of osteoclasts, the major agents of bone resorption, are controlled by osteoblasts. In this paper I provide direct evidence that osteoblasts are indeed able to alter the behaviour of osteoclasts. I used calcitonin (CT) to suppress the cytoplasmic activity of osteoclasts isolated on glass or plastic substrates, and found that, while isolated osteoclasts remain quiescent in CT for as long as the hormone is present, they regain activity when osteoblasts are added to the culture. ‘Escape’ from CT-induced quiescence could not be transmitted by supernatants from cultures of osteoblasts, was not due to inactivation of CT by osteoblasts, and did not occur if osteoblasts were separated from osteoclasts by a Millipore filter. When osteoblasts and osteoclasts were cultured together at low cell density in CT, I found that while those osteoclasts in the culture that remained isolated also remained inactive, osteoclasts that were in contact with osteoblasts showed a return to activity. This return to activity was most marked in the portion of osteoclast periphery in direct contact with an adjacent osteoblast. Although contact with osteoblasts did not abrogate the sensitivity of osteoclasts to added calcitonin, osteoclasts were found to escape inhibition by calcitonin at a rate proportional to the number of osteoblasts with which they were in contact.