Osteoclastic Bone Resorption by a Polarized Vacuolar Proton Pump

American Association for the Advancement of Science (AAAS) - Tập 245 Số 4920 - Trang 855-857 - 1989
Harry C. Blair1, Steven L. Teitelbaum1,2, Robert W. Ghiselli1, Stephen L. Gluck3
1Department of Pathology, Jewish Hospital, Washington University Medical Center, St. Louis, MO 63110.
2Shriners' Hospital for Crippled Children, St. Louis, MO 63130.
3Department of Medicine, Jewish Hospital at Washington University Medical Center, St. Louws, MO 63110.

Tóm tắt

Bone resorption depends on the formation, by osteoclasts, of an acidic extracellular compartment wherein matrix is degraded. The mechanism by which osteoclasts transport protons into that resorptive microenvironment was identified by means of adenosine triphosphate-dependent weak base accumulation in isolated osteoclast membrane vesicles, which exhibited substrate and inhibition properties characteristic of the vacuolar, electrogenic H + -transporting adenosine triphosphatase (H + -ATPase). Identify of the proton pump was confirmed by immunoblot of osteoclast membrane proteins probed with antibody to vacuolar H + -ATPase isolated from bovine kidney. The osteoclast's H + -ATPase was immunocytochemically localized to the cell-bone attachment site. Immunoelectron microscopy showed that the H + -ATPase was present in the ruffled membrane, the resorptive organ of the cell.

Từ khóa


Tài liệu tham khảo

BARON, R, EVIDENCE FOR A HIGH AND SPECIFIC CONCENTRATION OF (NA+,K+)ATPASE IN THE PLASMA-MEMBRANE OF THE OSTEOCLAST, CELL 46: 311 (1986).

BARON, R, 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, JOURNAL OF CELL BIOLOGY 101: 2210 (1985).

BARSHAVIT, Z, DEFECTIVE BINDING OF MACROPHAGES TO BONE IN RODENT OSTEOMALACIA AND VITAMIN-D DEFICIENCY - INVITRO EVIDENCE FOR A CELLULAR DEFECT AND ALTERED SACCHARIDES IN THE BONE-MATRIX, JOURNAL OF CLINICAL INVESTIGATION 72: 526 (1983).

BLAIR, H.C., ISOLATED OSTEOCLASTS RESORB THE ORGANIC AND INORGANIC COMPONENTS OF BONE, JOURNAL OF CELL BIOLOGY 102: 1164 (1986).

BROWN, D, STRUCTURE OF THE NOVEL MEMBRANE-COATING MATERIAL IN PROTON-SECRETING EPITHELIAL-CELLS AND IDENTIFICATION AS AN H+ATPASE, JOURNAL OF CELL BIOLOGY 105: 1637 (1987).

Cretin, A., Presse Médicale 59: 1240 (1951).

DEDUVE, C, LYSOSOMOTROPIC AGENTS, BIOCHEMICAL PHARMACOLOGY 23: 2495 (1974).

FALLER, L, MECHANISTIC ASPECTS OF GASTRIC [H++K+]-ATPASE, ANNALS OF THE NEW YORK ACADEMY OF SCIENCES 402: 146 (1982).

Fallon, M. D., Endocrine Control of Bone and Calcium Metabolism 8: 144 (1984).

Galloway, C. J., Proceedings of the National Academy of Sciences of the United States of America 80: 3334 (1983).

GLICKMAN, J, GOLGI MEMBRANES CONTAIN AN ELECTROGENIC H+ PUMP IN PARALLEL TO A CHLORIDE CONDUCTANCE, JOURNAL OF CELL BIOLOGY 97: 1303 (1983).

GLUCK, S, IMMUNOAFFINITY PURIFICATION AND CHARACTERIZATION OF VACUOLAR H+ATPASE FROM BOVINE KIDNEY, JOURNAL OF BIOLOGICAL CHEMISTRY 262: 15780 (1987).

GLUCK, S, AN ELECTROGENIC PROTON-TRANSLOCATING ADENOSINE-TRIPHOSPHATASE FROM BOVINE KIDNEY MEDULLA, JOURNAL OF CLINICAL INVESTIGATION 73: 1704 (1984).

Gluck, S., Proceedings of the National Academy of Sciences of the United States of America 79: 4327 (1982).

JONESEY, J, JOURNAL OF CLINICAL INVESTIGATION 51: 9 (1972).

MELLMAN, I, ACIDIFICATION OF THE ENDOCYTIC AND EXOCYTIC PATHWAYS, ANNUAL REVIEW OF BIOCHEMISTRY 55: 663 (1986).

Ohkuma, S., Proceedings of the National Academy of Sciences of the United States of America 79: 2758 (1982).

SIMONS, K, CELL-SURFACE POLARITY IN EPITHELIA, ANNUAL REVIEW OF CELL BIOLOGY 1: 243 (1985).

TEITELBAUM, S.L., RODENT PERITONEAL-MACROPHAGES AS BONE RESORBING CELLS, CALCIFIED TISSUE INTERNATIONAL 27: 255 (1979).