Mannose receptor C type 2 mediates 1,25(OH)2D3/vitamin D receptor-regulated collagen metabolism through collagen type 5, alpha 2 chain and matrix metalloproteinase 13 in murine MC3T3-E1 cells.

Vitamin D plays an important role in maintaining skeletal development and bone homeostasis. Although vitamin D has been extensively researched, the direct effect of 1,25(OH)2D3 on osteoblasts is unclear. To explore the 1,25(OH)2D3 action on murine osteoblasts, we performed tandem mass tag experiments on MC3T3-E1 cells treated with and without 1,25(OH)2D3. Three up-regulated proteins (MRC2, WWTR1 and RASSF2) related to bone metabolism were confirmed in this study. 1,25(OH)2D3 up-regulated the expression of MRC2 through vitamin D receptor. MRC2 affects collagen metabolism in osteoblasts. Combined with bioinformatics and parallel reaction monitoring analysis, we inhibited the expression of MRC2 to explore the relationship between MRC2 and collagens. Then we found MRC2 down-regulated COL5A2 and up-regulated MMP13. This study provides a protein profile of 1,25(OH)2D3-treated murine osteoblasts, reveals a newly discovered signaling axis (1,25(OH)2D3/VDR/MRC2/COL5A2 and MMP13), and explains the effect of 1,25(OH)2D3 on bone metabolism from a new perspective.