{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T14:27:34Z","timestamp":1792506454324,"version":"4.5.0"},"reference-count":30,"publisher":"National Academy of Sciences","issue":"10","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2001,5,8]]},"abstract":"<jats:p>\n                    Various genetic conditions produce dysfunctional osteoclasts\n resulting in osteopetrosis or osteosclerosis. These include human\n pycnodysostosis, an autosomal recessive syndrome caused by cathepsin K\n mutation, cathepsin K-deficient mice, and\n                    <jats:italic>mitf<\/jats:italic>\n                    mutant\n rodent strains. Cathepsin K is a highly expressed cysteine protease in\n osteoclasts that plays an essential role in the degradation of protein\n components of bone matrix. Cathepsin K also is expressed in a\n significant fraction of human breast cancers where it could contribute\n to tumor invasiveness. Mitf is a member of a helix\u2013loop\u2013helix\n transcription factor subfamily, which contains the potential\n dimerization partners TFE3, TFEB, and TFEC. In mice, dominant negative,\n but not recessive, mutations of\n                    <jats:italic>mitf<\/jats:italic>\n                    , produce\n osteopetrosis, suggesting a functional requirement for other family\n members. Mitf also has been found\u2014and TFE3 has been suggested\u2014to\n modulate age-dependent changes in osteoclast function. This study\n identifies cathepsin K as a transcriptional target of Mitf and TFE3 via\n three consensus elements in the cathepsin K promoter. Additionally,\n cathepsin K mRNA and protein were found to be deficient in\n                    <jats:italic>mitf<\/jats:italic>\n                    mutant osteoclasts, and overexpression of wild-type\n Mitf dramatically up-regulated expression of endogenous\n cathepsin K in cultured human osteoclasts. Cathepsin K promoter\n activity was disrupted by dominant negative, but not recessive, mouse\n alleles of\n                    <jats:italic>mitf<\/jats:italic>\n                    in a pattern that closely matches their\n osteopetrotic phenotypes. This relationship between cathepsin K and the\n Mitf family helps explain the phenotypic overlap of their corresponding\n deficiencies in pycnodysostosis and osteopetrosis and identifies likely\n regulators of cathepsin K expression in bone homeostasis and human\n malignancy.\n                  <\/jats:p>","DOI":"10.1073\/pnas.091479298","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:44:19Z","timestamp":1027680259000},"page":"5798-5803","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":190,"title":["Linking osteopetrosis and pycnodysostosis: Regulation of cathepsin K expression by the microphthalmia transcription factor family"],"prefix":"10.1073","volume":"98","author":[{"given":"G.","family":"Motyckova","sequence":"first","affiliation":[{"name":"Division of Pediatric Hematology\/Oncology, Dana\u2013Farber Cancer\r Institute and Children's Hospital, Harvard Medical School, Boston, MA\r 02115; Department of Bone and Cartilage Biology,\r SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406; and\r Department of Cardiology, University of Massachusetts\r Medical Center, Worcester, MA 01655"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. N.","family":"Weilbaecher","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology\/Oncology, Dana\u2013Farber Cancer\r Institute and Children's Hospital, Harvard Medical School, Boston, MA\r 02115; Department of Bone and Cartilage Biology,\r SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406; and\r Department of Cardiology, University of Massachusetts\r Medical Center, Worcester, MA 01655"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Horstmann","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology\/Oncology, Dana\u2013Farber Cancer\r Institute and Children's Hospital, Harvard Medical School, Boston, MA\r 02115; Department of Bone and Cartilage Biology,\r SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406; and\r Department of Cardiology, University of Massachusetts\r Medical Center, Worcester, MA 01655"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. J.","family":"Rieman","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology\/Oncology, Dana\u2013Farber Cancer\r Institute and Children's Hospital, Harvard Medical School, Boston, MA\r 02115; Department of Bone and Cartilage Biology,\r SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406; and\r Department of Cardiology, University of Massachusetts\r Medical Center, Worcester, MA 01655"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. Z.","family":"Fisher","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology\/Oncology, Dana\u2013Farber Cancer\r Institute and Children's Hospital, Harvard Medical School, Boston, MA\r 02115; Department of Bone and Cartilage Biology,\r SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406; and\r Department of Cardiology, University of Massachusetts\r Medical Center, Worcester, MA 01655"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. E.","family":"Fisher","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology\/Oncology, Dana\u2013Farber Cancer\r Institute and Children's Hospital, Harvard Medical School, Boston, MA\r 02115; Department of Bone and Cartilage Biology,\r SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406; and\r Department of Cardiology, University of Massachusetts\r Medical Center, Worcester, MA 01655"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2001,5]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.38.3.241"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1210\/edrv.20.3.0367"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1105786"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/8756-3282(85)90406-5"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.187.5.775"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01741984"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90429-T"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.8.22.2770"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1194-256"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/8756-3282(95)00080-W"},{"key":"e_1_3_3_11_2","first-page":"1871","volume":"147","author":"Nii A","year":"1995","unstructured":"A Nii, E Steingrimsson, N G Copeland, N A Jenkins, J M Ward Am J Pathol 147, 1871\u20131882 (1995).","journal-title":"Am J Pathol"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.23.13453"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.1999.14.10.1654"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.273.5279.1236"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02015392"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.2000.15.3.451"},{"key":"e_1_3_3_17_2","first-page":"5386","volume":"57","author":"Littlewood-Evans A J","year":"1997","unstructured":"A J Littlewood-Evans, G Bilbe, W B Bowler, D Farley, B Wlodarski, T Kokubo, T Inaoka, J Sloane, D B Evans, J A Gallagher Cancer Res 57, 5386\u20135390 (1997).","journal-title":"Cancer Res"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V88.7.2531.bloodjournal8872531"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/34681"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.4.2.167"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/36593"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.7.3597"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81569-X"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.14.3.301"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1997.4614"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1997.4631"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.18.12.6930"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1006\/excr.2000.4803"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.125.23.4607"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)65172-3"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.091479298","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,25]],"date-time":"2022-04-25T20:09:31Z","timestamp":1650917371000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.091479298"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,5]]},"references-count":30,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2001,5,8]]}},"alternative-id":["10.1073\/pnas.091479298"],"URL":"https:\/\/doi.org\/10.1073\/pnas.091479298","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,5]]},"assertion":[{"value":"2000-10-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2001-05-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}