1) Osteoporosis; 2) Electric Fields in tissues; 3) Transmembrane voltage functions

Living bone is constantly dissolved and reformed. (this doesn't occur in Dentine of teeth)
The dissolving is done by a special cell type: "osteoclasts" which have many nuclei per cell, and develop by fusion of macrophages. Osteoclasts secrete protein-digesting enzymes and acids into closed-off spaces between themselves and surfaces of bone.

The remaking of bone is done by a different cell type: Osteocytes = Osteoblasts.
These secrete new collagen fibers & somehow (?!) cause calcium phosphate to precipitate next to (but not inside) them.
It is not agreed = understood how osteocytes cause calcium phosphate to precipitate.
Among possible mechanisms, they might secrete calcium ions at locations where enzymes are splitting phosphate ions off from molecules like ATP (which also chelate calcium)

A very different possibility is that osteocytes might secrete some chemical that reduces the solubility product of calcium phosphate. Is this chemically possible? Does fluoride do this? It is well known that chelators like EDTA increase ion solubilities?
So is the reverse possible? Are actual chemicals known that do the reverse? Fluoride?
Please try to invent experiments that could detect (or DIS)prove this idea.

Imposing tension and/or compression on bone (somehow) stimulates increased strength. For example, tennis players develop stronger bones (and stronger muscles) in whichever arm (the right arm in right-handed tennis players).
Surgical removing either the radius or ulna from sheep, thereby doubling pressure on remaining leg bone, caused great increase in bone formation, as expected. But a surprise was that spongy bone formed on the outside surfaces of the remaining bone.

In all bones, trabeculi form preferentially along axes of maximum force; & if this axis is changed, that somehow causes new trabeculi to form parallel to the new axis of force.

Weakening of bone (osteoporosis) is a major medical problem for millions of Americans, especially older women, and indirectly causes hundreds of thousands of deaths. In principle, osteoporosis could either be caused by increased rates of destruction by osteoclasts or by decreased renewal of bone by osteocytes, or by a combination.
Another category of cause could be reduced sensitivity to stimulation by physical forces.


How do bone cells detect amounts, locations and directions of forces exerted on/in bones? One popular theory (for many decades) has been that bone might be a piezoelectric crystal (including quartz and sucrose) that generate electrical voltages when distorted in shape.

The good news for this theory is that bone (and cartilage) emits voltages when stressed. The bad new is that calcium phosphate has the wrong symmetry to be piezoelectric. (Ions need to be arranged such that distorting a crystal causes unequal shifts of negative ions relative to positive ions) (The need to lack "inversion symmetry”.

I suspect that bone voltages are caused by electroosmosis, in which negative sulfate ions are covalently linked to collagen by chains of sugar molecules, and only positive ions are able to be squeezed out by pressure. This is another way to produce osmotic pressure, without semi-permeable membranes! Textbooks have mostly forgotten about this. What Wikipedia says on these subjects illustrates how confusing it can be. (Especially the "talk" section) Whenever distortion produces a voltage, then conversely voltages will produce shape change or movements of parts. In piezoelectric lighters, force generates voltage, and in atomic force microscopy voltage produces movements / forces.

In a salt water environment, small voltages will quickly drain away. Thus neither piezoelectric or electroosmotic effects can produce long-lasting electric currents. Also, increasing pressure produces exactly the same effect as decreasing tension. In effect, both these sources of voltage detect what amounts to the first derivative of shape changes.
Question for discussion: Would/Should ossification be stimulated more by a steady force or by a rapid vibration? Consider the implication for inducing bone growth by exercises or by wires emitting electric voltages. Should alternating current or direct current be used?

Hint: Actual hospitals used direct current, but probably should have used alternating current.

Resting potentials occur in all cell types, not just nerves, muscles and oocytes.
A third or more of cells' ATP energy gets used up by the sodium pump generating and maintaining the high K+ in the cytoplasm and high Na+ outside the plasma membrane.
Doesn't it seem this distribution of ions, and/or the 50-100 millivolt positive outside voltage produced by this huge expenditure of energy must be serving some important functions, that nobody has discovered yet?

Tissue culture cells crawl directionally in response to small voltages.
>= volt per millimeter =millivolt per micrometer.
Which is roughly one resting potential per cell length.
Epithelial cells crawl toward the negative electrode, so do osteocytes, so do nerve fibers.
Osteoclasts and other macrophages crawl toward the positive electrode?
Mesenchymal cells line up perpendicular to an external electric fields.
(Fungal mycelia grow exactly parallel to voltages, I happened to notice. Why??)

QUESTION FOR DISCUSSION: Whether this opposite electrical response of osteoclasts versus osteocytes is causally related to their bone-destruction versus bone construction?

Different possible reasons / mechanisms by which a voltage difference might alter cell movement or forces between one side of a cell and the other. If we assume that plasma membranes have much lower electrical conductivity than the cytoplasm, therefore externally imposed voltage gradients will be much less steep inside cells as compared with in the surrounding medium (I think?). Try to figure this out.
So which side of a cell will be depolarized, and which side will be hyper-polarized by an externally imposed voltage? Suppose one cell type contracts more strongly in response to depolarization: will that side become the front? What difference in effects of depolarization would cause osteoclasts to crawl in the opposite direction as osteoblasts?
Do you suppose depolarization is causally linked to bone formation, or destruction?

Imagine if some positively charged membrane protein were pulled along cell surfaces accumulating near the side of each cell nearest the negative electrode. Would you consider that electrophoresis? What if accumulation of such a protein caused cells to crawl toward higher concentrations? ..crawl away? … detach?
Argue pro or con if directionality of movements could be why cells have resting potentials.

PS: Some danger of electrocution is hard to avoid in studies of voltage effects on cells.


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