Biology 446    Unsolved Problems Fall 2011




Below is the URL of a YouTube site apparently intended for medical students. It makes every standard mistake. Each and every statement is either over-simplified, flat wrong, or is an arbitrary definition of a cell or arrangement of cells. It couldn't be better as a codification of current scientific failure to understand how ossification works, using definitions of words as a substitute for understanding of mechanisms. This site is one of a series. The worst of their innumerable mistakes is the claim that cartilage "can only grow by apposition", in the sense of addition of cells at the surface. Actually, most cartilage growth is by internal expansion.

Although it is true that discoveries of mechanisms often require researchers to invent new vocabulary, and to make new distinctions between phenomena that had previously seemed to be the same as each other, new knowledge isn't created by new words. The motto of the Royal Society is "Nullus in Verbo". The meaning of this Latin phrase is that we should seek facts not words. It expressed a wish, in the mid 1600s, to escape from Aristotelian ways of thinking. I wish I knew Latin phrases for "Equations aren't always so great, either." "Cloning genes and knocking out their transcription don't necessarily tell you everything you need to know, either." Nor does the identification of stimulatory molecules, but they are often very useful for medical treatment of either an excess or a deficiency. For every process that goes on in the body, I think there are at least two diseases: One caused by not enough, or too low a rate, of the phenomenon; and the other caused by too much, or too high a rate of that same phenomenon. If you can discover the cause of the "Not enough" disease, that probably will lead you toward a cure for the "Too much" disease.

The following web site is quite funny. The mispronunciations are deliberate, I assume.

The following web site has very good time lapse videos (speeded up a few hundred times) showing macrophages fusing with each other to form giant, multinucleated osteoclasts.

Notice that the biggest osteoclasts passes through a stage of being the same shape as Australia! Surely an accident; but I will be on the look out for osteoclasts shaped like other continents.

This site shows actual photographs, not drawings. These photographs show pieces of bone in tissue culture, together with macrophages and osteoclasts.

Rich, A., and A.K. Harris (1981). Anomalous preferences of macrophages for roughened and hydrophobic substrata. J. Cell Sci. 50: 1-7. This paper reports experiments on differences between macrophages and (all?) other cell types in the body. Nobody has discovered whether osteoclasts differ in these same special properties. It would be fairly easy to do, and differences in cell locomotion between osteoclasts and osteocytes could be very important. They respond in opposite ways to electric fields, but that's not in this paper.

This next web site shows a slick set of animations of phenomena that may or may not match what really happens.

The animations were made by a pharmaceutical company. There really is good evidence that the large size of osteoclasts allows them to seal off a volume of space, between themselves and bone surfaces, into which hydrogen ions ("acid") and proteolytic enzymes are secreted and accumulate. This is something they "show" happening in their animation. But please understand that these are drawings, not photographs. I have never found photographs of bone formation, and have failed to make time lapse films or videos of bone formation. It's a good question why this shouldn't be just as easy as photographing osteoclasts in the process of destroying bone.

Notice that this site claims that what osteocytes (which they prefer to call "osteoblasts") mainly do is to secrete a mixture of substances they call "Osteoid". This is supposed to be a mixture of type I collagen (which is 1/3 of bone by weight and 1/2 of bone by volume) combined with some unknown chemical that causes calcium phosphate to precipitate out of solution, even at concentrations of calcium ions multiplied by concentrations of phosphate ions that are below the saturation concentration [called the "ion product", something else one learns about in thermodynamics].

A central question, sort of a holy grail for this whole field, is whether a crystallization-inducing substance, does exist or can exist, that can cause salt precipitation at concentrations less than saturation. The situation is related to super-saturation. An example of super-saturation would be if we put some crystals of calcium chloride near some crystals of sodium phosphate. I am assuming both these salts are much more soluble in water than calcium phosphate is; but we should find out for sure. As calcium ions are released from one of these salts, and phosphate salts are released by the other salt, then eventually a region of saturation or super-saturation should form, where the concentration of calcium ions multiplied by the concentration of phosphate ions becomes as large as (or larger than) would occur if we had put calcium phosphate in a test tube full of water, and left it for a long time to equilibrate. Crystals can be caused to form from a super-saturated solution either by nucleation with a crystal, by nucleation with some other substance (analogous to a boiling chip), or spontaneously (when ion concentrations get so darned large that the get embarrassed about it, or something like that.)

The following web site seems to promise this particular holy grail:

Really, it's a study of locations of calcium phosphate crystal formation relative to the sub-microscopic striations that all type I collagen fibers have. It's a good paper, but the title promises more than the paper actually delivers. The laboratory of N A J M Sommerdijk in Eindhoven in the Netherlands leads the world in research on formation of all sorts of skeletons, including the calcium carbonate of mollusks and echinoderms, and the silica of diatoms. Their specialty is how precipitation of these materials is initiated. I can't find much about how the ions of these materials get concentrated together at high enough concentrations to allow their precipitation to be initiated. You can find dozens of papers by this group by Googling "google scholar", and then typing in Sommerdijk.

They have at least two you-tube web sites illustrating their hypotheses, which they state as facts.


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