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These defects are caused in part by impaired cartilage mineralization and vascularization of the chondro\u2010osseous junction. Blood vessel invasion of mineralized cartilage is an essential step in endochondral ossification, providing access for cells that degrade cartilage as well as those that form bone. Vascular endothelial growth factor (VEGF) was shown to be a key regulator of this process when infusion of a dominant negative VEGF receptor effectively blocked vascular invasion and endochondral ossification in the growth plates of juvenile mice. Here, we show that the active metabolite of vitamin D 1\u03b1,25\u2010dihydroxyvitamin D<jats:sub>3<\/jats:sub> [1\u03b1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub>] directly stimulates transcription of mRNAs encoding VEGF121 and \u2212165 isoforms in the CFK2 chondrogenic cell line. Enhanced VEGF expression also was evident in growth plate chondrocytes and osteoblasts in the tibia of juvenile mice treated systemically with 1\u03b1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub>. This was seen in conjunction with enhanced expression of matrix metalloproteinase (MMP) 9, which activates VEGF stored in the cartilage matrix, in osteoclastic cells adjacent to the chondro\u2010osseous junction. The alterations in VEGF and MMP\u20109 expression were accompanied by enhanced vascular invasion of mineralized cartilage, as assessed by CD31 immunoreactivity. These results provide evidence that 1\u03b1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub> signaling stimulates VEGF and MMP\u20109 gene expression and promotes neovascularization of the epiphyseal growth plate in vivo through increased availability of active growth factor.<\/jats:p>","DOI":"10.1359\/jbmr.2002.17.9.1604","type":"journal-article","created":{"date-parts":[[2006,4,27]],"date-time":"2006-04-27T05:28:41Z","timestamp":1146115721000},"page":"1604-1612","source":"Crossref","is-referenced-by-count":89,"title":["1\u03b1,25\u2010Dihydroxyvitamin D<sub>3<\/sub> Promotes Vascularization of the Chondro\u2010osseous Junction by Stimulating Expression of Vascular Endothelial Growth Factor and Matrix Metalloproteinase 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