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Foreman in the bone factory


Etsuko Abe and colleagues have made an unexpected discovery, as they report in Cell (115, 151–162; 2003). They show that thyroid-stimulating hormone (TSH) — best known for its role in stimulating the secretion of thyroid hormones in mammals — also regulates the turnover of bone.

During adult life, old bone is continually resorbed and replaced by new bone. These 'remodelling' events must be tightly coupled in both space and time. If, for instance, the activity of bone-resorbing cells (called osteoclasts) exceeds that of bone-depositing cells (osteoblasts), the result is osteoporosis — brittle, weakened bones. The scanning electron micrograph opposite shows the spongy nature of such bones, with many large holes visible (blue). A variety of factors can cause osteoporosis, one of which is high levels of thyroid hormone. Such high levels produce low TSH levels, but it has generally been thought that TSH has nothing to do with the reduction in bone density. Abe et al. now find otherwise.

The authors started by generating mice that lack the cellular receptor that responds to TSH. They found, not surprisingly, that the mice showed little thyroid activity and stunted growth (one of the thyroid's main functions is to ensure proper growth). But the animals also had short, overly light bones. The bones showed severe osteoporosis as well as localized dense patches, suggesting that bone formation and resorption had, to some extent, become spatially separated. Feeding the mice thyroid extracts, to restore their levels of thyroid hormones, increased body weight, but not bone weight or length. This hints that the effects of TSH loss on bone are direct, rather than occurring via thyroid hormones. In support of this, the TSH receptor is found on both osteoclasts and osteoblasts.

Abe et al. also discovered that bone was remodelled much more quickly in the mutant mice than in normal animals, and that more osteoclasts and osteoblasts were formed. These and other findings suggest that TSH usually functions to inhibit both of these cell types. The authors have also begun to define the distinct intracellular signalling pathways by which TSH prevents the formation and survival of osteoclasts and the formation of osteoblasts. The conclusion is that when TSH is missing, bone remodelling loses a crucial overseer.


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Tromans, A. Foreman in the bone factory. Nature 425, 909 (2003).

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