ON THE MECHANISM OF ACTION OF PARATHORMONE¹

Cell-mediated extracellular acidification and bone resorption: evidence for a low pH in resorbing lacunae and localization of a 100-kD lysosomal membrane protein at the osteoclast ruffled border.

“…Hence, one is led to the view that bone resorption could occur entirely within an extracellular lysosome-like compartment, acidified and equipped with lysosomal enzymes directionaUy secreted by the osteoclast. The low pH prevailing in the bone-resorbing compartment would be sufficient to dissolve the mineral phase of bone matrix (21,30,44) and would provide optimal conditions for the degradative action of acid hydrolases on the organic phase of bone matrix (44). Considering the extracellular bone-resorbing compartment as the functional equivalent of a secondary lysosome where digestion of bone matrix could be complete, residues from this extracellular digestion could diffuse through cell membranes as through lysosomes and would not require endocytosis for further digestion inside the osteoclasts.…”

“…It has repeatedly been proposed, but never demonstrated, that this compartment is acidified in order to allow the dissolution of the mineral constituents of bone as well as to provide an optimal pH for acid hydrolase activity (19,28,30,31,44).…”

“…First, early studies by Neuman et al (30,31) and by Vaes (44) demonstrated that the parathyroid hormone-induced stimulation of bone resorption in organ culture is associated with increased production of lactate and citrate by the explants and results in the acidification of the culture medium. Second, the observation of increased concentration of Yttrium in bone resorp-FIGURE I General view of an osteoclast after localization of arylsulfatase.…”

Effect of Saliva-Parotin-a on Serum Citric Acid

“…Other possible organs for the site of its action are the intestine, the liver and bones. Bones are known to produce a large amount of citric acid (Kenny et al, 1959) and supply it into blood stream (Neuman et al, 1956;Martin et al, 1958;. Possibility exists that the effects of salivaparotin-A on calcium metabolism (Ito and Okabe, 1959) or on the development of bone tissues in vitro (Ito et al, 1961) are mediated by the effect on citric acid metabolism in bone cells.…”

“…Possibility exists that the effects of salivaparotin-A on calcium metabolism (Ito and Okabe, 1959) or on the development of bone tissues in vitro (Ito et al, 1961) are mediated by the effect on citric acid metabolism in bone cells. This is a very interesting problem in view of the fact that parathyroid hormone has an effect on citrate production in bones (Neuman et al, 1956;Martin et al, 1958;Lekan et al, 1959;Schooley and Otero, 1960). However, the problem whether the changes in serum citrate is related to those in the rate of the production of citric acid by bone cells remains to be proved.…”