"Red blood cells are about 95% hemoglobin, which makes sense because their main job is to ferry the oxygen that sustains the body’s tissues. Researchers have detected hemoglobin in an assortment of other cell types, including neurons, lung cells, and
immune cells called macrophages, but so far they haven’t found conclusive evidence that the protein performs a vital role for these cells.

Scientists had not previously reported finding hemoglobin in chondrocytes. In 2017, however, pathologist Feng Zhang of the Fourth Military Medical University was studying bone development in young mice when he noticed some unusual blobs in chondrocytes
from the animals’ growth plates, the cartilaginous layers near the ends of some bones that allow them to lengthen. Not only did the structures resemble red blood cells, but they were also rich in hemoglobin. Zhang joined forces with cell biologist
Qiang Sun of the Chinese Academy of Medical Sciences and other researchers to better understand what these mysterious objects were and what they were doing in the animals’ cartilage.

Oxygen is scarce in the growth plates, which don’t have their own blood supply. Yet chondrocytes divide rapidly, indicating they must have mechanisms to function amid low oxygen levels. The researchers wondered whether hemoglobin helped chondrocytes
survive. To test that hypothesis, the scientists turned to genetically altered mice that produce fewer functional hemoglobin molecules than normal. Analyzing the animals’ cartilage, they found that large numbers of chondrocytes perished in the growth
plates.

Next, the scientists repeated the experiment in rodents with reduced amounts of hemoglobin only in their chondrocytes. Once again, the cells died in droves in the growth plates, the researchers revealed earlier this month in Nature.

To probe how hemoglobin might protect chondrocytes, the team grew unaltered and genetically modified growth plate cells in a low-oxygen environment. Unlike hemoglobin-depleted cells, normal chondrocytes readily released oxygen under these conditions, and
they were less likely to die, the scientists determined.

The scientists think the hemoglobin-containing blobs they identified in the growth plates function as oxygen depots for chondrocytes, absorbing the scarce molecule from their surroundings and then releasing it to meet cells’ needs. If so, they would
represent the second adaptation that enables chondrocytes to withstand low oxygen levels. Researchers had previously found another mechanism that activates an alternative metabolic pathway for breaking down sugars that doesn’t require oxygen. “The
beauty of this paper is that it shows an additional mechanism that chondrocytes use to protect themselves” from low oxygen levels, Schipani says.

Like youth, growth plates are fleeting. In humans, they form before birth and disappear around puberty. But chondrocytes persist throughout life elsewhere in the body, including in the joints, where they help maintain the cartilage. These cells, too, are
remote from the blood supply and have to survive oxygen scarcity. The team has found the hemoglobin-harboring structures in chondrocytes from other parts of mice’s bodies, including the ribs and feet, as well as in human knee cartilage.

Still unknown is whether hemoglobin enables chondrocytes in these locations to survive oxygen scarcity like it does in growth plates. The work also raises the possibility that a shortfall of hemoglobin in chondrocytes contributes to conditions in which
bone growth is impaired, such as certain types of dwarfism, Ono says. “This [paper] opens up the opportunity for many other studies.”"

https://www.science.org/content/article/more-red-blood-cells-depend-hemoglobin-surprising-study-cartilage-reveals

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