Control of matrix synthesis in isolated bovine chondrocytes by extracellular and intracellular pH

The effects of extracellular and intracellular pH on matrix synthesis by isolated bovine chondrocytes were studied using radioisotope incorporation (35SO4 and 3H proline) and fluorescence techniques. Matrix synthesis exhibited a bimodal relation with decreased extracellular pH; with slight reductions (7.4 > pH > 7.1), synthesis increased (by up to 50%), whereas in more acidic media (pH < 7.1), synthesis was inhibited by up to 75% of control levels. The pHi was largely unchanged with extracellular acidity over the range producing stimulation of matrix synthesis but fell when exposed to the more acidic media shown to have an inhibitory action on matrix synthesis. The inhibition of matrix synthesis by lactic acid addition was unaffected by the lactic acid transporter alpha-CHC, suggesting H+ transport by this pathway is small. Direct imposition of a sustained intracellular acidosis (pHi = 6.65) using ammonium prepulse with amiloride inhibited matrix synthesis by about 20%. These results show that matrix synthesis by chondrocytes was affected by extracellular pH, an action which could not be entirely explained by changes to pHi.