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.

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