BoneKEy Reports | BoneKEy Watch
Mitochondrial function, intracellular ATP levels and bone resorption
DOI:10.1038/bonekey.2012.250
Little is known about the role of mitochondria in mature osteoclasts. Miyazaki et al. reveal here that osteoclasts have more mitochondria and higher intracellular ATP levels compared with either osteoblasts or bone marrow-derived monocyte/macrophage precursor cells (BMMs).
Expression of Bcl-xL, an anti-apoptotic protein, increased intracellular ATP levels in osteoclasts more than nine times, and mRNA levels were significantly lower in osteoclasts than in BMMs. This suggests that osteoclast maturation involves downregulation of Bcl-xL, which is then associated with a reduction in intracellular ATP.
The relevance of this became clearer during the study of osteoclasts from Tfam knockout mice, which have an osteoclast-specific conditional knockout that prevents them from producing ATP. The mice demonstrated reduced growth and their osteoclasts showed accelerated apoptosis, but, surprisingly, the bone-resorbing activity of those osteoclasts increased significantly compared to osteoclasts from wild-type mice. Further experiments showed that a rise in extracellular ATP inhibited the function of osteoclasts.
When the osteoclasts from aging mice were studied, they were found to have even lower levels of intracellular ATP and their ability to resorb bone was enhanced.
Editor’s comment: This study proposes that ATP levels within mitochondria regulate osteoclast apoptosis and therefore their ability to perform efficient bone resorption. These observations also suggest that mitochondrial dysfunction, which might occur with aging, could result in enhanced bone resorption and osteoporosis.
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