UNASSIGNED: We have previously shown that ablation of either the @entity70140 or @entity10749 gene, encoding @entity70140 and @entity10749 ( @entity10749 ) respectively, lead to hyperosteoidosis but that their chondrocyte- and osteoblast-derived matrix vesicles (MVs) are able to initiate mineralization. In contrast, the double ablation of @entity70140 and @entity10749 completely abolish initiation and progression of skeletal mineralization. We argued that MVs initiate mineralization by a dual mechanism: @entity70140 -mediated intravesicular generation of Pi and @entity4613 transporter-mediated influx of Pi . To test this hypothesis, we generated @entity19 with @entity15137 -driven cre-mediated ablation of @entity70141 , hereafter referred to as @entity70141 , alone or in combination with a @entity70140 gene deletion. @entity70141 ( @entity15137 / @entity15137 ) @entity19 did not show any major @entity66 , while severe @entity85 were observed in the [ @entity70140 (-/-) ; @entity70141 ( @entity15137 / @entity15137 ) ] double knockout @entity19 that were more pronounced than those observed in the @entity70140 (-/-) @entity19 . Histological analysis of [ @entity70140 (-/-) ; @entity70141 ( @entity15137 / @entity15137 ) ] bones showed growth @entity854 with a shorter @entity1184 chondrocyte zone and extensive hyperosteoidosis. The [ @entity70140 (-/-) ; @entity70141 ( @entity15137 / @entity15137 ) ] skeleton displayed significantly decreases in BV/TV%, trabecular number and bone mineral density, as well as decreased stiffness, decreased strength, and increased post-yield deflection compared to @entity70140 (-/-) @entity19 . Using atomic force microscopy we found that    80% of [ @entity70140 (-/-) ; @entity70141 ( @entity15137 / @entity15137 ) ] MVs were devoid of mineral in comparison to    50% for the @entity70140 (-/-) MVs and    25% for the WT and @entity70141 ( @entity15137 / @entity15137 ) MVs. We also found a significant decrease in the number of MVs produced by both @entity70140 (-/-) and [ @entity70140 (-/-) ; @entity70141 ( @entity15137 / @entity15137 ) ] chondrocytes. These data support the involvement of @entity70141 in the initiation of skeletal mineralization and provide compelling evidence that @entity70140 function is involved in MV biogenesis.

Skeletal Mineralization Deficits and Impaired Biogenesis and Function of Chondrocyte-Derived Matrix Vesicles in @entity70140 (-/-) and @entity70140 / XXXX Double Knockout @entity19 .

@entity66 :: ('MESH:D004194', 'Disease') :: ['phenotypic abnormalities'] @entity70141 :: ('20515(Tax:10090)', 'Gene') :: ['Pi T-1', 'Pit1', 'Slc20a1', 'Pi t1'] @entity10749 :: ('11647(Tax:10090)', 'Gene') :: ['tissue-nonspecific alkaline phosphatase', 'TNAP', 'Alpl'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity1184 :: ('MESH:D006984', 'Disease') :: ['hypertrophic'] @entity4613 :: ('D010710', 'Chemical') :: ['phosphate'] @entity15137 :: ('12824(Tax:10090)', 'Gene') :: ['col2a1', 'col2'] @entity70140 :: ('237928(Tax:10090)', 'Gene') :: ['PHOSPHO1', 'Phospho1'] @entity854 :: ('MESH:D018376', 'Disease') :: ['plate abnormalities'] @entity85 :: ('MESH:D009140', 'Disease') :: ['skeletal deformities']
@entity70141 :: (20515(Tax:10090),Gene) :: ['Pit1']
