The following hypothesis attempts to explain the puzzling fact that osteoblasts--the bone-forming cells--seem to be the target cells of parathyroid hormone (PTH), the prostaglandins, and 1, 25-dihydroxyvitamin D3 (1, 25 (OH) 2D3), the bone-resorbing hormones. This hypothesis combines some old and new physiological, biochemical, and morphological data, and ascribes to the osteoblasts a pivotal role in bone resorption.

PTH has been shown to have a large number of effects on osteoblasts or" osteoblast-like" cells including:(a) stimulation of adenylate cyclase activity resulting in a cyclic AMP (cAMP) surge [1, 2];(b) rapid activation of cyclic AMP-dependent protein kinase [3];(c) inhibition of collagen synthesis [4];(d) inhibition of alkaline phosphatase activity [1, 5];(e) stimulation of calcium uptake [6, 7]; and (f) production of cell shape changes resulting in less tight packing of the cells, observed both in calvaria and in culture [8, 9]. On the other hand, there is little evidence so far that osteoclasts possess PTH receptors or respond to PTH directly. There is accumulating evidence that circulating mononuclear cells (monocytes) are osteoclast precursors and can resorb devitalized bone in culture [10, 12], but PTH has no effect on the chemotactic migration or the resorbing activity of these cells. Moreover, PTH does not seem tO be essential for normal osteoclastic activity and bone remodeling since these functions are retained in parathyroidectomized newborn rats [13]. Furthermore, no PTH-related defect can be implicated in osteoclast malfunctions associated with osteopetrosis [14]. Other bone-resorbing humoral factors have osteoblasts as their targets. Prostaglandins stimulate cyclic AMP accumulation in osteoblast-like cells, and there is a remarkably close correlation between