{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T13:39:25Z","timestamp":1791121165808,"version":"4.1.0"},"reference-count":41,"publisher":"Rockefeller University Press","issue":"2","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2000,10,16]]},"abstract":"<jats:p>c-src deletion in mice leads to osteopetrosis as a result of reduced bone resorption due to an alteration of the osteoclast. We report that deletion\/reduction of Src expression enhances osteoblast differentiation and bone formation, contributing to the increase in bone mass. Bone histomorphometry showed that bone formation was increased in Src null compared with wild-type mice. In vitro, alkaline phosphatase (ALP) activity and nodule mineralization were increased in primary calvarial cells and in SV40-immortalized osteoblasts from Src\u2212\/\u2212 relative to Src+\/+ mice. Src-antisense oligodeoxynucleotides (AS-src) reduced Src levels by \u223c60% and caused a similar increase in ALP activity and nodule mineralization in primary osteoblasts in vitro. Reduction in cell proliferation was observed in primary and immortalized Src\u2212\/\u2212 osteoblasts and in normal osteoblasts incubated with the AS-src. Semiquantitative reverse transcriptase-PCR revealed upregulation of ALP, Osf2\/Cbfa1 transcription factor, PTH\/PTHrP receptor, osteocalcin, and pro-alpha 2(I) collagen in Src-deficient osteoblasts. The expression of the bone matrix protein osteopontin remained unchanged. Based on these results, we conclude that the reduction of Src expression not only inhibits bone resorption, but also stimulates osteoblast differentiation and bone formation, suggesting that the osteogenic cells may contribute to the development of the osteopetrotic phenotype in Src-deficient mice.<\/jats:p>","DOI":"10.1083\/jcb.151.2.311","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:45:41Z","timestamp":1027701941000},"page":"311-320","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":259,"title":["Decreased C-Src Expression Enhances Osteoblast Differentiation and Bone Formation"],"prefix":"10.1083","volume":"151","author":[{"given":"Marilena","family":"Marzia","sequence":"first","affiliation":[{"name":"aDepartment of Histology and General Embryology, University La Sapienza, 00161 Rome, Italy"},{"name":"bDepartment of Experimental Medicine, University La Sapienza, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie A.","family":"Sims","sequence":"additional","affiliation":[{"name":"hDepartments of Orthopaedics and of Cell Biology, Yale University, New Haven, Connecticut 06510"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Voit","sequence":"additional","affiliation":[{"name":"dDepartment of Experimental Medicine, University of L'Aquila, 00161 L'Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Migliaccio","sequence":"additional","affiliation":[{"name":"aDepartment of Histology and General Embryology, University La Sapienza, 00161 Rome, Italy"},{"name":"cDepartment of Medical Physiopathology, University La Sapienza, 00161 Rome, Italy"},{"name":"dDepartment of Experimental Medicine, University of L'Aquila, 00161 L'Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Taranta","sequence":"additional","affiliation":[{"name":"aDepartment of Histology and General Embryology, University La Sapienza, 00161 Rome, Italy"},{"name":"eIstituto Dermopatico dell'Immacolata, 00167 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Bernardini","sequence":"additional","affiliation":[{"name":"eIstituto Dermopatico dell'Immacolata, 00167 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tullio","family":"Faraggiana","sequence":"additional","affiliation":[{"name":"bDepartment of Experimental Medicine, University La Sapienza, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiyuki","family":"Yoneda","sequence":"additional","affiliation":[{"name":"fDivision of Endocrinology and Metabolism, University of Texas Health Science Center, San Antonio, Texas 78284-7877"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory R.","family":"Mundy","sequence":"additional","affiliation":[{"name":"fDivision of Endocrinology and Metabolism, University of Texas Health Science Center, San Antonio, Texas 78284-7877"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendan F.","family":"Boyce","sequence":"additional","affiliation":[{"name":"gDepartment of Pathology, University of Texas Health Science Center, San Antonio, Texas 78284-7877"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Baron","sequence":"additional","affiliation":[{"name":"hDepartments of Orthopaedics and of Cell Biology, Yale University, New Haven, Connecticut 06510"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Teti","sequence":"additional","affiliation":[{"name":"dDepartment of Experimental Medicine, University of L'Aquila, 00161 L'Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2000,10,16]]},"reference":[{"key":"2023072902312974000_Alamaetal1997","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1006\/phrs.1997.0227","article-title":"Antisense oligonucleotides as therapeutic agents","volume":"36","author":"Alama","year":"1997","journal-title":"Pharmacol. 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