REGULATION OF OSTEOCLASTIC BONE-RESORPTION BY GLUCOSE

Osteoclasts degrade bone by pumping molar quantities of HCI to dissolv e the calcium salts of bone, an energy intensive process evidently sup ported by abundant mitochondria. This is the first study to directly e xamine the ability of various metabolites to serve as potential energy sources for osteoclastic bone resorption. Glucose, and to a lesser ex tent lactate, supported osteoclastic bone degradation, However, fatty acids (palmitate, myristate and stearate), essential amino acids plus 20 mM alanine, or ketone bodies (acetoacetate, beta-hydroxybutyrate an d alpha-ketoglutarate) did not support bone degradation. Resorption de clined to 10-30% of glucose controls when fatty acids or ketoacids wer e substituted for glucose. Resorption was glucose concentration depend ent, with maximal activity at similar to 7 mM (K-M similar to 3 mM). G lucose transport was linear for similar to 15 minutes, specific for D- glucose, and inhibited by cytochalasin B. Osteoclasts cultured on bone transported glucose at almost twice the rate of those off bone (V-max , 23 versus 13 nmols/ mg/min, respectively) and medium acid accumulati on paralleled glucose uptake, while the K-M was unchanged. We conclude that glucose is the principal energy source required for bone degrada tion. Further, characteristics of glucose transport are consistent wit h the hypothesis that fluctuations in serum glucose concentration are an important component in regulation of osteoclastic bone degradation. (C) 1997 Academic Press.