Cartilage degeneration in alkaptonuria is associated with altered primary cilia

What is it about?

Alkaptonuria is a rare inherited disease resulting from a deficiency of the enzyme homogentisate 1,2-dioxygenase which leads to an accumulation of homogentisic acid (HGA). One primary characteristic of alkaptonuria is severe cartilage degeneration, similar to that observed in osteoarthritis. Alkaptonuria is associated with changes in cartilage cell shape and composition, and we show that these changes also affect the primary cilia. The primary cilium is a single immotile organelle present in the majority of cells. This membrane-bound structure can protrude from the cell and forms a signalling hub which is key to various cellular signalling responses. One such cilia-associated signalling pathway which plays a major role in the proper function of cartilage cells is hedgehog. We show that cartilage cells from patients with alkaptonuria exhibit a defective response to hedgehog, and that this is due to disease-related changes in the primary cilium.

Featured Image

Why is it important?

This defective signalling is likely to contribute to the development of cartilage degeneration in alkaptonuria and identifies the primary cilium as a novel target for treatment of alkaptonuria.

Perspectives