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

Role of osteoblasts in hormonal control of bone resorption - a hypothesis

Introduction Vitamin D is generally accepted as being essential for life in higher animals (278). It is one of the most important biological regulators of calcium and phosphorus (406) metabolism. Along with the two peptide hormones PTH and calcitonin, vitamin D is responsible for the minute-to-minute as well as the day-to-day establishment and maintenance of calcium homeostasis. The substance vitamin D, or cholecalciferol, was first identified through the nutritional studies of Sir Edward Mellanby (243), which identified rickets as a disease state resulting from a deficiency of vitamin D, as well as through the biochemical/chemical studies of McCollum and co-workers (242), who demonstrated that there was more than one fat-soluble vitamin. Together these studies established a deficiency state, namely rickets, which was attributable to the newly discovered, nutritionally important fat-soluble component, vitamin D. In retrospect, however, the most important discovery related to the appreciation by Huldschins...

The vitamin D endocrine system: steroid metabolism, hormone receptors, and biological response (calcium binding proteins).

This study examines the osteoblastic properties of the established human osteosarcoma cell line Saos-2. Saos-2 cells inoculated into diffusion chambers, which were implanted i.p. into nude mice, produced mineralized matrix in 4 of 6 chambers at 8 weeks. In 5 of 6 chambers there was a strong positive alkaline phosphatase reaction. In culture the alkaline phosphatase levels increased with time and cell density, reaching very high levels at confluence: 4–7 µmol/mg protein/min. The cells show a sensitive adenylate cyclase response to parathyroid hormone, 50% effective dose = 2.8 nm, which increases with cell density and is further raised by dexamethasone treatment. They also exhibit typical binding of 1-25-dihydroxyvitamin D 3 to 3.2S receptor protein with an apparent K d of 0.21 nm; the numbers of sites per cell were 3,300 at 50,000 cells/cm 2 and 1,800 at 280,000 cells/cm 2 . The presence of osteonectin was visualized with a monoclonal antibody which revealed a reticular pattern on the cell surface. Osteonectin was also detected in the medium by Western blots, migrating at around M r 40,000 in nonreduced gels and M r 44,000 in reduced gels. The Saos-2 cells thus possess several osteoblastic features and could be useful as a permanent line of human osteoblast-like cells and as a source of bone-related molecules.

https://cancerres.aacrjournals.org/content/canres/47/18/4961.full.pdf

Characterization of a human osteosarcoma cell line (Saos-2) with osteoblastic properties.

Geographic variation in breast cancer mortality in the United States: a hypothesis involving exposure to solar radiation.

Rapidly forming apatitic mineral in an osteoblastic cell line (umr 106-01 bsp)

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1016/0014-5793%2880%2980744-7

Receptors for 1,25(OH)2-vitamin D3 enriched in cloned osteoblast-like rat osteogenic sarcoma cells

1,25-Dihydroxyvitamin D3 receptor in a cultured human breast cancer cell line (MCF 7 cells).

Malignant and benign human breast tumours as well as rabbit breast tissue were examined for specific receptors for 1,25-dihydroxyvitamin D3 using competitive binding studies and sucrose density gradient analysis. Classical high affinity, low capacity receptors for 1,25-dihydroxyvitamin D3 were found in breast and node tissue in seven of ten patients with breast cancer and in all three patients with benign neoplasms. An inflammatory breast mass showed no binding. Similar receptors were found in breast tissue from pregnant and lactating rabbits. Taken with other recent data, these results suggest that 1,25-dihydroxyvitamin D3 may activate calcium transport in the malignant as well as in the normal lactating breast.

R. J. Frampton

Papers

Receptors for 1,25(OH)2-vitamin D3 enriched in cloned osteoblast-like rat osteogenic sarcoma cells

1,25-Dihydroxyvitamin D3 receptor in a cultured human breast cancer cell line (MCF 7 cells).

Normal and malignant breast tissue is a target organ for 1,25-(0H)2 vitamin D3.