Like all the other sytems in your body, the skelatal system does not appear out of nowhere. It takes careful planning and balance.

Dynamic Bone 

Bone consists of blood vessels, cortical bone, and cancellous bone. Bones, like your skin, regenerate themselves constantly. They do this by a process of making new mineralized bone, also called bone matrix (hydroxyapatite) while destroying old bone matrix at the same time. Two types of cells are invovled in this process: osteoblasts and osteoclasts.

     Osteoblasts, the first type, are the cells that form new bone matrix^[1]. They are activated by the Wnt channeling system and told to form from messenchymal stem cells into messenchymal bone cells which mature into osteoblasts (as seen in the picture on the right)^[2]. Osteoblasts move down the blood vessels to any part of the bone matrix that needs repair (see diagram at bottom). The bone matrix, the hard part, is made of mineralized extra cellular matrix.

     Osteoclasts, which are activated by the DKK1 ligand, (as seen in the diagram to the left) break down old bone matrix. They do this by releasing acids and hydrolytic enzymes that break down the matrix to form a space for new mineralized bone to form. 

     The activity of these two types of cells needs to be kept in balance like a see-saw. If the number of osteoblasts is getting too high, the body will produce more osteoclasts so the bone does not become too thick (Van Buchem's syndrome) or too thin (osteoporosis)^[3].

     In Van Buchem's Syndrome, mutations in LRP5 block the normal activity of DKK1 which leads to unusually high numbers of osteoblasts. This in turn leads to too much bone matrix production which leads to heavily mineralized bones (denser bones).

Missense Mutations

Van Buchem's Syndrome (home page)

Page Authors: Emmie Ryan and Julie Swihart