Sodium transport systems in human chondrocytes II. Expression of ENaC, Na+/K+/2Cl(-) cotransporter and Na+/H+ exchangers in healthy and arthritic chondrocytes

In this article, the second of two, we continue our studies of sodium-depen dent transport systems in human cartilage from healthy individuals and with osteoarthritis (OA) and rheumatoid arthritis (RA). We demonstrate the pres ence of the epithelial sodium channel (ENaC), previously undescribed in cho ndrocytes. This system is composed of three subunits, alpha, beta and gamma . We have shown that the human chondrocytes express at least the alpha and the beta subunit of ENaC. The expression of these subunits is altered in ar thritic chondrocytes. In RA samples the quantity of alpha and beta is signi ficantly higher than in control samples. On the other hand, ENaC alpha and beta subunits are absent in the chondrocytes of OA cartilage. Human chondro cytes also possess three isoforms of the Na+/H+ exchanger (NHE), NHE1, NHE2 and NHE3. The NHE system is composed of a single protein and is believed t o participate in intracellular pH regulation. Furthermore, our studies indi cate that at least one isoform of the electroneutral Na+/K+/2Cl(-) cotransp orter (NKCC) is present in human chondrocytes. There are no obvious variati ons in the relative expression of NHE isoforms or NKCC between healthy and arthritic cartilage. Our data suggests that chondrocytes from arthritic car tilage may adapt to changes in their environmental sodium concentration thr ough variations in ENaC protein levels. ENaC is also likely to serve as a m ajor sodium entry mechanism, a process that, along with cytoskeletal protei ns, may be part of mechanotransduction in cartilage.