This article is really interesting and disturbing (Ronden et al., 1997):
http://66.102.1.104/scholar?num=100&hl=en&lr=&q=cache:zJY4MxPFnO4J:sinoas.com/journal/journal02/PDF/132-1/Modulation%2520of%2520arterial%2520thrombosis%2520tendency%2520in%2520rats%2520by%2520vitamin%2520K%2520and%2520its%2520side%2520chains.pdf+
(Note that the "+" should be tagged onto the end of that url. The pdf links were bad links.)
The authors found that phylloquinone (vitamin K1) increased the tendency to form thrombi in rats, and they induced some form of damage to increase the thrombogenic tendency. When you read the first part of the article, it sounds like there's no effect on the coagulation cascade. But there is, and it's not reflected in the serum coagulation factor levels. That's what's disturbing. They didn't find a similar effect for vitamin K2. I know they are different and have different tissue distributions (vitamin K1 ends up mostly in the liver, and vitamin K2 is more blood-borne and lipoprotein-bound), but I don't buy that vitamin K2 has no thrombogenic potential. The authors are actually, as I explain, not even saying that it doesn't increase the thrombogenicity. Implicit in their hypothesis is the idea that its thrombogenicity is offset by an induction of monocyte/macrophage apoptosis. The authors go on to hypothesize that there may be some effect, locally in the endothelial cells, of vitamin K1 on tissue factor release or on some other pathway involved in initiating the coagulation cascade.
The authors make a really interesting suggestion to account for the reduction in thrombogenicity by vitamin K2 and the increase from vitamin K1. They note that vitamin K2 has been shown to cause osteoclast apoptosis and that, given that osteoclasts and monocytes share common precursor cells, the apoptotic effect of vitamin K2 on osteoclasts might extend to macrophages. Their hypothesis is that vitamin K2 would initiate apoptosis either in the osteoclast precursors, thereby both helping to limit bone breakdown by osteoclasts and to limit the maturation of some osteoclast precursor cells into pro-thrombotic macrophages, or initiate apoptosis after some of the precursor cells have differentiated into thrombogenic macrophages. So what they're saying is that both vitamin K1 and vitamin K2 have some kind of thrombogenic effect, perhaps some local effect on the blood vessels that can't be detected by looking at clotting factor levels, and that that effect of vitamin K2 may be offset by the "macrophage-apoptotic" effect (cell death in macrophages).
I know the bisphosphonates cause osteoclast apoptosis, but this effect of vitamin K2 is not something to be excited about, in my opinion. Here are all the studies citing this one (http://scholar.google.com/scholar?num=100&hl=en&lr=&cites=1718746073486648067), and it looks like they missed the point about vitamin K1 (and by implication of the authors, vitamin K2) producing thrombogenicity by an unknown mechanism. This study raises some really serious concerns about using vitamin K supplements for "bone-building." The osteoclast apoptosis effect is not a sophisticated mechanism, really, and it's not, as the authors have said, very specific to osteoclasts.
This article I chose is actually not that great an illustration of this [Sohel Yamamoto et al., 2007 (http://www.ncbi.nlm.nih.gov/pubmed/17610478)], but the authors talk in the article about the epithelial cell and macrophage-associated markers (CD68, for example, as they refer to, is a macrophage protein marker) in those esophageal tumor cells in that person (these are markers that are generally specific for those cell types but are also found in some precursor cells, like stem cells, or in tumor cells). There are stem cells in the esophagus and stomach (they mention the "primitive basal cells of the bronchial mucosa," and the esophageal or gastric cells are similar and normally would differentiate into "mucosal epithelial cells"). The point is that those stem cells can have certain similarities to the epithelial cells they would normally differentiate into but also may have some markers in common with osteoclasts and macrophages (the authors refer to the prostate, biliary tree, breast, intestine, and pancreas as sites of these kinds of tumors, and there are different versions of "epithelial cells" in all those sites). Something like vitamin K2, to the extent that it could induce osteoclast apoptosis and macrophage apoptosis, could conceivably also affect cell types with some proteins that are characteristic of "epithelial" differentiation.
What I'm saying is that there's this phenomenon whereby some cell types (pluripotent, undifferentiated stem-cell-like cells in some parts of the body or slightly "de-differentiated" epithelial cells in other parts) can become osteoclast-like. And it isn't a vague, cell-type-nonspecific effect of something, like vitamin K2, that may act on osteoclasts. There's a pretty clear connection of osteoclasts to other, specific cell types, meaning that the knowledge, among some researchers, of the cell types that are or can be osteoclast-like (in terms of differentiation markers) is not "shrouded in mystery," so to speak. It's relatively clear, even if that article I chose doesn't show it very effectively.
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