Central control of bone remodeling by neuromedin U
Bone remodeling, which is affected in osteoporosis, comprises two phases: bone formation by matrix-producing osteoblasts and bone resorption by osteoclasts. The demonstration that the anorexigenic hormone leptin inhibits bone formation through a hypothalamic relay suggests that other molecules that affect energy metabolism in the hypothalamus could also modulate bone mass. Neuromedin U is an anorexigenic neuropeptide that acts independently of leptin through poorly defined mechanisms.
A recent study [1] shows that neuromedin U-deficient mice have high bone mass owing to an increase in bone formation; this is more prominent in male mice than female mice. Physiological and cell-based assays indicate that neuromedin U acts in the central nervous system, rather than directly on bone cells, to regulate bone remodeling. Notably, leptin- or sympathetic nervous system–mediated inhibition of bone formation was abolished in neuromedin U-deficient mice, which show an altered bone expression of molecular clock genes such as Per1 and Per2 which are mediators of the inhibition of bone formation by leptin (see Osteoscoop issue N° 34 “Molecular bases of leptin control of bone formation”). Moreover, treatment of wild-type mice with a natural agonist for the neuromedin U receptor decreased bone mass.
Collectively, these results suggest that neuromedin U may be the first central mediator of leptin-dependent regulation of bone mass identified to date. Given the existence of inhibitors and activators of neuromedin U action, these results may influence the treatment of diseases involving low bone mass, such as osteoporosis.
- Sato S et al. Nat Med. 2007;13:1234-1240.
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