THE CRUCIAL ROLE OF THE WNT SYSTEM IN BONE REMODELLING.

The maintenance of bone mass is critically dependent on the balance between bone formation by osteoblasts and bone resorption by osteoclasts, processes in which osteocytes play also an important role. The activities of these bone cells are regulated by a variety of endocrine and paracrine factors of which sex steroids, parathyroid hormone, 1.25(OH)2-vitamin D3, glucocorticoids, retinoids and thyroid hormones are the most well known systemic factors. To the long list of locally acting factors belong cytokines and growth factors. This list was extended some 15 years ago by the discovery of the very important role of the WNT signalling system for the maintenance of bone mass. The first evidence of its role was the findings that mutations in the LRP5 gene, encoding a co-receptor in WNT-signaling, could result in either gain or loss of bone mass, i.e. either high bone mass or osteoporosis. This was a most unexpected observation since no indications existed prior to this discovery that the WNT signalling system had a role in bone remodeling. Since then, many observations have been made demonstrating the important role of different WNTs in regulating bone formation and resorption. Interestingly, some of these findings have demonstrated that trabecular and cortical bone are regulated by different mechanisms. It is the aim of the present overview to give the readers an insight into the WNT signalling system and its role in bone remodeling.