INTRACELLULAR SIGNALING IN THE BONE-RESORBING CELLS

Several reports have recently been published on the pathways that cells employ to produce messenger molecules in response to Ca2+ mobilizing signals. This review provides an insight into the mechanisms responsible for the control of Ca2+ homeostasis in the osteoclast. Osteoclasts respond to the inhibiting factors calcitonin and elevated extracellular calcium concentration ([Ca2+](o)) with rapid increases of the [Ca2+](i), an important intracellular signal that induces activation of several Ca2+-dependent cellular substrates. These factors are likely to activate phospholipase C-associated receptors, which not only produce [Ca2+](i) elevations, but also activate the protein kinase C, a serine/threonine phosphorylating enzyme. Other factors act as Ca2+ mobilizing signals in osteoclasts, but their role in the cell function is not yet fully understood. Thus, platelet activating factor produces [Ca2+](i)elevations, but it is thought to stimulate osteoclast function. additionally, bone matrix proteins show distinct effects on [Ca2+](i)in chicken and in mammalian osteoclasts. In the former they induce [Ca2+](i) decreases, whilst in the latter the same proteins produce [Ca2+](i) transient elevations. Whether or not the two pathways cause diverse, species-specific effects on osteoclast function is at present unknown. These results highlight several complexity in the ability of osteoclasts to manipulate [Ca2+](i) in response to stimuli relevant for the bone resorbing activity.