Channel Surfing: Time to Get Physical with OA?

It's not very often you get a room full of OA biology researchers who haven't heard of YFP (your favourite protein) before. But every once in a while, a new one comes up, just like it did today at the Chondrocyte Channels session. 

What is a Pannexin? Just as we have been getting used to the fact that chondrocytes have membrane channels, there's a new one on the block. But it's not a full channel, it's a HEMI-channel! Sounds interesting, but we have no idea what goes in or out of the pannexin hemi-channels in chondrocytes, nor what might be their function in chondrocytes.

Today, Frank Beier showed that one of the three known pannexins in the family (Pannexin 3) is increased in post-traumatic OA, but not in age-associated OA. And, if you knock out the pannexin 3 gene in two different mouse models of OA, the mice are protected from post-traumatic OA but they still get age-associated OA.

The discovery adds to other OA-related channel discoveries in recent years. Ali Mobasheri reviewed the "channelome" (all expressed membrane channels) of chondrocytes, as well as the "surfaceome" (all proteins expressed on or in cell and organellar surfaces). This is an area of massive data expansion that is showing us new ways in which chondrocytes function and maintain homeostasis by talking to their environment. The concept is particularly interesting since most chondrocytes aren't in direct contact with other cells, unlike most other tissues.

Even more exciting is that many pharmaceuticals currently on the market have been designed for cell membrane channels (think calcium channel blockers, sodium channel blockers, etc), and are just waiting to be exploited through repurposing efforts. This is a great new avenue for OA research with much work to be done at the basic/translational biology and clinical levels.

What is fascinating is the mounting biological evidence that OA isn't a single disease, even though the common "OA" label is routinely used to describe multiple different mechanisms for developing joint damage. Look no further than today's example of Pannexin 3 being relevant for post-traumatic OA, but not likely so for age-associated OA. It suggests that physical stimuli may be a driver in some types of OA, but not all, so different treatment approaches may be needed according to OA phenotype. 

We need to be more disciplined about how we categorize OA in the clinic and in research studies and stop calling everything "OA" and just leaving it at that. Doing so may increase our chances of finally getting long-overdue treatments to our patients with the most common (yet most maligned) arthritis.

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