1,25(OH)2D3 regulates collagen quality in an osteoblastic cell culture system

The active form of vitamin D, 1,25(OH)2D3, has a broad range of effects on bone, however, its role in the quality of bone matrix is not well understood. In this study, using an osteoblastic cell (MC3T3-E1) culture system, the effects of 1,25(OH)2D3 on collagen cross-linking and related enzymes, i.e., lysyl hydroxylases (LH1-3) and lysyl oxidases (LOX, LOXL1-4), were examined and compared to controls where cells were treated with cholecalciferol or ethanol. When compared to the controls, gene expressions of LH1, LH2b and LOXL2 were significantly upregulated by 1,25(OH)2D3 up to 72 h of culture. In addition, hydroxylysine (Hyl), Hyl aldehyde (Hylald), Hylald-derived cross-links and a total number of cross-links of collagen were significantly higher and the cross-link maturation was accelerated in the 1,25(OH)2D3 treated group. These results demonstrate that 1,25(OH)2D3 directly regulates collagen cross-linking in this culture system likely by upregulating gene expression of specific LH and LOX enzymes.