Knee Deep in Water: Aquaporin 9 and Cartilage Damage.

Not much is currently understood about the factors responsible for the progression of osteoarthritis (OA). Clinical studies have identified a variation in Dickkopf-1 (DKK1) levels with progression of OA. We analysed DKK1 targets in human osteoarthritic cartilage and identified Aquaporin 9 (AQP9) as a candidate of interest. The aquaporin family of water channels comprise 13 family members which either solely transport water or water and other solutes, like AQP9. Aquaporins play a role in energy metabolism and cellular osmotic balance, cell movement and motility, glycerol metabolism, water resorption and osteoclast differentiation. In OA, the normally stable articular chondrocyte differentiates towards hypertrophy. Aquaporins may be important in the control of chondrocyte shape, modulating chondrocyte changes that occur during the hypertrophy process that accompanies cartilage damage. Our data indicate that Aqp9 is expressed in human OA cartilage and highly expressed in the prehypertrophic zone of the mouse cartilage growth plate. Using a genetically modified mouse model where Aqp9 is deleted, we show that these mice are protected against the cartilage degradation that occurs with age. These mice are also protected against cartilage loss induced after surgical destabilization of the knee joint. Our data suggests that Aqp9 is important in chondrocyte hypertrophy and may represent a novel therapeutic target to slow down the progression of OA.