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EphrinB2 is a receptor tyrosine kinase expressed by osteoblasts and growth plate chondrocytes that promotes osteoblast differentiation and inhibits osteoclast formation. We investigated the role of ephrinB2 in endochondral ossification using osterix-Cre (Osx1Cre) targeted gene deletion. Neonatal Osx1Cre.EfnB2\u0394\/\u0394 mice exhibited a transient osteopetrosis. This was demonstrated by increased trabecular bone volume with a high content of growth plate cartilage remnants and increased cortical thickness, but normal osteoclast numbers within the primary spongiosa. On closer examination, osteoclasts at the growth plate of Osx1Cre.EfnB2\u0394\/\u0394 mice had abnormal morphology and expressed low levels of tartrate-resistant acid phosphatase; this was not observed in more mature bone. Transmission electron microscopy revealed a lack of sealing zones and poor attachment of Osx1Cre.EfnB2\u0394\/\u0394 osteoclasts to growth plate cartilage. Osteoblasts at the growth plate were also poorly attached and impaired in their ability to deposit osteoid. By 6 months of age, trabecular bone mass, osteoclast morphology and osteoid deposition by osteoblasts in Osx1Cre.EfnB2\u0394\/\u0394 mice was normal compared to controls. Cultured chondrocytes from Osx1Cre.EfnB2\u0394\/\u0394 neonatal mice showed impaired support of osteoclastogenesis but no significant change in RANKL 9 (Tnsf11) levels; instead Adamts4 levels were significantly lowered. Immunohistochemical staining of control neonates showed a population of early hypertrophic chondrocytes positive for ADAMTS4, these cells were not positively stained in Osx1Cre.EfnB2\u0394\/\u0394 mice. This suggests that Osx1Cre-expressing cells, including hypertrophic chondrocytes, are dependent on EphrinB2 for their production of cartilage degrading enzymes, including Adamts4 and this may be required for attachment of osteoclasts and osteoblasts to the cartilage surface during endochondral ossification.<\/jats:p>","DOI":"10.1242\/dev.125625","type":"journal-article","created":{"date-parts":[[2016,1,12]],"date-time":"2016-01-12T03:19:11Z","timestamp":1452568751000},"source":"Crossref","is-referenced-by-count":18,"title":["Chondrocytic EphrinB2 promotes cartilage destruction by osteoclasts in endochondral ossification"],"prefix":"10.1242","author":[{"given":"Stephen","family":"Tonna","sequence":"first","affiliation":[{"name":"St. Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia"},{"name":"The University of Melbourne, Department of Medicine at St. Vincent's Hospital, Fitzroy, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid J.","family":"Poulton","sequence":"additional","affiliation":[{"name":"St. Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farzin","family":"Taykar","sequence":"additional","affiliation":[{"name":"St. Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia W. 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