Monogenic ion channelopathies of the skeleton

Although ion channels are intuitively more related to the generation of action potentials, they can influence skeletal cells, development, and homeostasis in different ways as demonstrated in this review. All major skeletal cell types, chondrocytes, osteoblasts, osteocytes, and osteoclasts, can be involved in the pathogenesis and often the interaction of these different defects is incompletely understood. Connexin 43 and TRPV4, two of the mentioned membrane proteins, predominantly conduct calcium ions and are the basis of a whole spectrum of skeletal phenotypes. While connexin 43 seems to regulate the function of osteoblasts and osteocytes, TRPV4 is crucial for chondrocytes. The other two examples are chloride-transporting membrane proteins ANO5 and ClC-7, which can cause gnathodiaphyseal dysplasia and osteopetrosis, respectively. Whereas the function of ANO5 is largely unknown, the role of ClC-7 in bone resorbing osteoclasts has been investigated in great detail.