Alhough we think of our bones as solid and permanent, they are actually rebuilt throughout our lives. A team of scientists at the Weizmann Institute in Rehovot have now revealed how cells that work at remodeling bones play a direct part in the ongoing renewal of another system - the blood. Their findings, which may lead to improvements in bone marrow transplantation and a better understanding of diseases involving bone or blood renewal, were published in the June issue of Nature Medicine.
Bones are really two systems in one. The cavities inside are filled with spongy bone marrow, in which stem cells divide and their daughter cells differentiate into all kinds of blood cells, including large numbers of immune cells for the body's defense. The hematopoietic (blood-creating) stem cells, which can give rise to any kind of blood cell, reside in special "stem cell niches" in the bones' inner walls. Inside these sheltered nurseries, the stem cells remain undifferentiated; with the help of other nearby cells, they hang on to their juvenile qualities. Only when they leave the niches do they morph into specialized blood cells, possibly becoming immune cells for fighting infection or cells for blood clotting and healing. They can even respond to calls for help from organs such as the liver, migrating through the bloodstream to assist.
The inner walls of the bones are also sites of intensive reconstruction. While one type of cell, the osteoblast, is busy building bone, its partner, the osteoclast, breaks it down and reassimilates the material. Osteoclasts are formed when several cells (which themselves originate from hematopoietic stem cells) fuse together at a signal from the osteoblasts, and the two work together in a sort of "urban renewal" scheme.
The Weizmann Institute team headed by Prof. Tsvee Lapidot of the immunology department, which included Dr. Orit Kollet and colleagues, found that the bone-dismantling osteoclasts are instrumental in releasing hematopoietic stem cells into the bloodstream. As they wear away the bone, they allow stem cells out of the niches and into the bloodstream. Although some hematopoietic stem cells can always be found circulating in the blood, when there is bleeding or inflammation in the body more stem cells are needed to deal with the situation. The study showed that the bone marrow's response to the body's call for help involves stepping up production of osteoclasts, putting machinery that normally operates at a leisurely pace into high gear. The osteoclasts not only clear away bone, they also break up "nurturing" substances in the niche that attract and hold the stem cells to that spot, allowing more stem cells into the blood.
The team carried out their research on mice, including some developed in the lab of Prof. Ari Elson of the molecular genetics department, in which the osteoclasts carried a mutation that rendered them only partially functional in the young females. They found abnormally low stem-cell levels in the blood of these mice even when they tried to encourage their mobilization, giving solid evidence of the connection. In normal mice, using a compound that stimulates osteoclast formation, they were able to boost osteoclast levels and release stem cells into the blood in a variety of stress situations.
This finding may have implications for bone marrow transplants: The drugs given today to donors to increase the supply of stem cells in their bloodstream before they are harvested for transplantation cause the release of many other mature cells as well. Injecting the osteoclast-promoting substance into the mice, on the other hand, resulted in an increase mainly in stem cell release. These findings add a new dimension to our understanding of the processes of renewal and breakdown in the body. In some forms of osteoporosis, autoimmune arthritis and cancer that has metastasized to the bone, for instance, osteoclasts demolish bone faster than it's built up. This study suggests the effects of such an imbalance may reach well beyond the bone.
PAYING ATTENTION TO COLOR
If someone, somewhere hadn't thought to make team uniforms the same color, we might be stuck watching soccer matches with only two players and a referee. It is that color coding, say Johns Hopkins University psychologists, that allows spectators, players and coaches to overcome humans' natural inability to track more than three objects at a time.
"We've known for some time that human beings are limited to paying attention to no more than three objects at any one time," says Justin Halberda, assistant professor of psychological and brain sciences in the university's' Zanvyl Krieger School of Arts and Sciences, who published his article in the July issue of Psychological Science.
"We report the rather surprising result that people can focus on more than three items at a time if those items share a common color," he said. "Our research suggests that the common color allows people to overcome the usual limit, because the 'color coding' enables them to perceive the separate individuals as a single set."
Thus: Miami Heat fans perceive their five white-jerseyed players as a unit in action against five blue-shirted Dallas Mavericks. England's football faithful can track their white-shirted field players against Sweden's yellow-garbed 10. (Since soccer goalies wear different colors than field players, though, fans of both clubs may have to think a moment before remembering which keeper goes with which team.)