Expression analysis of nha-oc/NHA2: a novel gene selectively expressed in osteoclasts.
Bone resorption by osteoclasts is required for normal bone remodeling and reshaping of growing bones. Excessive resorption is an important pathologic feature of many diseases, including osteoporosis, arthritis, and periodontitis [Abu-Amer, Y. (2005). Advances in osteoclast differentiation and function. Curr. Drug Targets. Immune. Endocr. Metabol. Disord. 5, 347-355]. On the other hand, deficient resorption leads to osteopetrosis which is characterized by increased bone mass and may lead to bone deformities or in severe cases to death [Blair, H.C., Athanasou, N.A. 2004. Recent advances in osteoclast biology and pathological bone ddresorption. Histol. Histopathol. 19, 189-199; Del Fattore, A., Peruzzi, B., Rucci, N., Recchia, I., Cappariello, A., Longo, M., Fortunati, D., Ballanti, P., Iacobini, M., Luciani, M., Devito, R., Pinto, R., Caniglia, M., Lanino, E., Messina, C., Cesaro, S., Letizia, C., Bianchini, G., Fryssira, H., Grabowski, P., Shaw, N., Bishop, N., Hughes, D., Kapur, R.P., Datta, H.K., Taranta, A., Fornari, R., Migliaccio, S., and Teti, A. 2006. Clinical, genetic, and cellular analysis of 49 osteopetrotic patients: implications for diagnosis and treatment. J. Med. Genet. 43, 315--325]. Recently, we identified a gene, nha-oc/NHA2, which is strongly up regulated during RANKL-induced osteoclast differentiation in vitro and in vivo. nha-oc/NHA2 encodes a novel cation/proton exchanger that is strongly expressed in osteoclasts. The purpose of this work was to further validate the restricted expression of nha-oc/NHA2 in osteoclasts by in situ hybridization. Our results showed that nha-oc is expressed predominantly in bone. In the head, expression was found in the supraoccipitale bone, calvarium, mandible, and maxilla. Furthermore, nha-oc positive cells co-express the osteoclast markers TRAP and cathepsin k, confirming nha-oc/NHA2 osteoclast localization. However, only a subset of cathepsin k-expressing cells is positive for nha-oc/NHA2, suggesting that nha-oc is expressed by terminally differentiated osteoclasts.
Pham
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Department of Cytokine Biology, Forsyth Institute, 140 The Fenway, Boston, MA 02115, USA.
Purcell
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Morse
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Stashenko
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Battaglino
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RA
D000135:Acid Phosphatase / Q000235:genetics; D000818:Animals; D017920:Antiporters / Q000235:genetics*; D001842:Bone and Bones / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D056657:Cathepsin K; D002403:Cathepsins / Q000235:genetics; D002454:Cell Differentiation; D015870:Gene Expression; D007527:Isoenzymes / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D010010:Osteoclasts / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D053245:RANK Ligand / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D000071681:Tartrate-Resistant Acid Phosphatase; D014018:Tissue Distribution
D017920:Antiporters; D007527:Isoenzymes; C526786:NHA2 protein, mouse; D053245:RANK Ligand; D012333:RNA, Messenger; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase; D002403:Cathepsins; D056657:Cathepsin K; C534132:Ctsk protein, mouse
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