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Accordingly, the collagen matrix in Smad4 mutants is disorganized, but also hypomineralized. Primary osteoblasts from Smad4 mutant mice do not mineralize in vitro in the presence of BMP2 or Wnt3a; and Smad4 mutant mice fail to accrue new bone following systemic Dkk1 inhibition. Consistent with impaired biological responses to canonical Wnt, Smad4 ablation causes \u03b2-catenin cleavage and Lrp5 depletion, associated with increased caspase-3 activity and apoptosis. In summary, Smad4 regulates maturation of skeletal collagen, osteoblast survival, and is required for matrix forming responses to both BMP2 and canonical Wnt.<\/jats:p>","DOI":"10.1242\/jcs.131953","type":"journal-article","created":{"date-parts":[[2013,9,5]],"date-time":"2013-09-05T04:46:34Z","timestamp":1378356394000},"source":"Crossref","is-referenced-by-count":25,"title":["Embryonic ablation of osteoblast <i>Smad4<\/i> interrupts matrix synthesis in response to canonical wnt signaling and causes an osteogenesis imperfecta-like phenotype"],"prefix":"10.1242","author":[{"given":"Valerie S","family":"Salazar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Zarkadis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Norris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan K","family":"Grimston","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Mbalaviele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Civitelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2013,1,1]]},"reference":[{"key":"2021042613132250600_b1","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/S0006-291X(02)02951-0","article-title":"Activated \u03b2-catenin induces osteoblast differentiation of C3H10T1\/2 cells and participates in BMP2 mediated signal transduction.","volume":"301","author":"Bain","year":"2003","journal-title":"Biochem. 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