Pathways regulating bone resorption

Published on January 19, 2015   40 min
0:00
Osteoclasts are among the most remarkable cells in the body. In this lecture, in addition to outlining their key regulatory pathways, I want to address some aspects of osteoclast biology that might be less well known, with a special focus on the roles of the fundamental parameters, oxygen tension, and pH.
0:22
If you want to see osteoclasts in action, a good place to start is actually to look at erupting teeth in the developing jaw. In this image, you can see adult teeth embedded in the jaw, and milk teeth protruding from the gum above. The developing adult teeth that are embedded in the jawbone have to make their way through the jawbone in order to erupt and serve their function.
0:48
This image shows, in higher power, the developing, erupting adult tooth surrounded by the concave bone. Lining the bone, you can see a number of large cells is the osteoclast. And these are in the process of eroding away the bone of the jaw, the alveolar bone, in order to make way for the tooth.
1:11
At higher power, we see the row of osteoclasts on the bone's surface. And we see that each osteoclast is embedded in a concavity in the bone. This is the process of bone resorption. In juveniles, such as the specimen we're seeing here, osteoclasts may be quite frequent.
1:34
However, in adult bone, osteoclasts occur far less commonly. But, for example, if we look at this section of a human finger bone, there's only a very small area, highlighted here, in which osteoclast activity is evident.
1:53
We see here a large multinucleated osteoclast, again, which has created an impressive cavity in the surface of the bone, which is now at the beginning stages of being infilled.
2:10
This image shows the impressive destruction that can be wrought by a single osteoclast, and emphasizes the need for very tight control of the formation and function of these cells. The requirement for close control of osteoclast function is further illustrated in this set of scanning electron micrographs.
2:36
This image shows a section across human vertebral bone. It's from the third lumbar vertebra. The marrow and the cells have been removed to reveal the bone architecture. You can see that in this healthy 30-year-old individual, the trabecular bone comprises of thick, interconnected plates that are mechanically strong enough to resist the forces applied to the bone during life.
3:08
At the same scale, this is third lumbar vertebra from a 71-year-old woman. And we see that those thick plates have disappeared, and all that's left are these rather thin, spindly elements of bone which can break with minimal trauma.
3:29
Zooming in again, we see that the erosion of these bone elements has occurred as the result of uncontrolled osteoclast activity. The strata of bone in the center of the image here is pitted with very many osteoclast resorption lacunae.
3:53
If this process were to have continued, then the trabecular element in question would have become perforated, as we see in this image. Again, the osteoclastic resorption pits are clearly evident, leading to a large space, or porosity in the bone, and resulting in significant mechanical weakness.
4:15
Osteoclasts arise from haematopoietic stem cells, which differentiate into myeloid precursors, and then into pre-osteoclasts, which fuse, initially to form a quiescent osteoclast, which under appropriate conditions can then become activated and form resorption pits. Once the osteoclast has done its job, it might revert to becoming a quiescent osteoclast, or it could undergo apoptosis and simply be disposed of. It's possible also that quiescent osteoclasts that don't have the opportunity to undertake bone resorption might also directly apoptose, and we'll deal with some of these mechanisms a little bit later on.
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Pathways regulating bone resorption

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