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However, the molecular mechanisms that regulate POC and SOC formation are different. We recently demonstrated that Prolyl Hydroxylase Domain-containing Protein 2 (<jats:italic>Phd2<\/jats:italic>) is a key mediator of vitamin C effects on bone. We investigated the role of <jats:italic>Phd2<\/jats:italic> on endochondral ossification of the epiphyses by conditionally deleting the <jats:italic>Phd2<\/jats:italic> gene in osteoblasts and chondrocytes. We found that the deletion of <jats:italic>Phd2<\/jats:italic> in osteoblasts did not cause changes in bone parameters in the proximal tibial epiphyses in 5 week old mice. In contrast, deletion of <jats:italic>Phd2<\/jats:italic> in chondrocytes resulted in increased bone mass and bone formation rate (normalized to tissue volume) in long bone epiphyses, indicating that <jats:italic>Phd2<\/jats:italic> expressed in chondrocytes, but not osteoblasts, negatively regulates secondary ossification of epiphyses. <jats:italic>Phd2<\/jats:italic> deletion in chondrocytes elevated mRNA expression of hypoxia-inducible factor (HIF) signaling molecules including <jats:italic>Hif-1\u03b1<\/jats:italic>, <jats:italic>Hif-2\u03b1<\/jats:italic>, <jats:italic>Vegfa<\/jats:italic>, <jats:italic>Vegfb<\/jats:italic>, and <jats:italic>Epo<\/jats:italic>, as well as markers for chondrocyte hypertrophy and mineralization such as <jats:italic>Col10<\/jats:italic>, <jats:italic>osterix<\/jats:italic>, alkaline phosphatase, and bone sialoprotein. These data suggest that <jats:italic>Phd2<\/jats:italic> expressed in chondrocytes inhibits endochondral ossification at the epiphysis by suppressing HIF signaling pathways.<\/jats:p>","DOI":"10.1038\/srep35748","type":"journal-article","created":{"date-parts":[[2016,10,24]],"date-time":"2016-10-24T09:26:50Z","timestamp":1477301210000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Prolyl Hydroxylase Domain-Containing Protein 2 (Phd2) Regulates Chondrocyte Differentiation and Secondary Ossification in Mice"],"prefix":"10.1038","volume":"6","author":[{"given":"Shaohong","family":"Cheng","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Aghajanian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheila","family":"Pourteymoor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catrina","family":"Alarcon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Subburaman","family":"Mohan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,10,24]]},"reference":[{"key":"BFsrep35748_CR1","doi-asserted-by":"crossref","unstructured":"Long, F. & Ornitz, D. 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