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. Author manuscript; available in PMC: 2014 Jan 1.
Published in final edited form as: J Bone Miner Res. 2013 Jan;28(1):56–72. doi: 10.1002/jbmr.1738

Figure 2. DMP1 regulation of FGF-23 in osteoblasts.

Figure 2

(A) Transfection of TMob cells with normal Dmp1, and resultant over-expression, reduced Fgf-23 mRNA expression significantly. In contrast, transfection of TMob cells with proteinase resistant Dmp1 had no effect on Fgf-23 mRNA expression in the TMob cells, suggesting that DMP1 proteolysis is essential to regulate Fgf-23 mRNA production. In accord, transfection of TMob cells with the C-terminal DMP1 fragment significantly decreased Fgf-23 mRNA expression, supporting the role of DMP1 proteolysis in regulation of Fgf-23 mRNA. (B) Serial transfection of TMob cells with Dmp1 and Pcsk2 (PC2) and Sgne1 (7B2) resulted in Western blot evidence of a significant increase in C-terminal and N-terminal DMP1 fragments, and a consequent decrease in the intact DMP1, consistent with 7B2•PC2 mediation of DMP1 proteolysis as a possible factor in regulation of Fgf-23 mRNA production. (C) Transfection of TMob cells with Sgne1 RNAi had no effect on Dmp1 mRNA production, but resulted in a significant decrease in the C-terminal and N-terminal DMP1 fragments, and a consequent increase in the intact DMP1, consistent with diminished proteolysis, further supporting a role for DMP1 cleavage in 7B2•PC2 regulation of Fgf-23 mRNA production. (D) Transfection of TMob cells with Sgne1 (7B2) RNAi had no effect on Bmp1 mRNA, when compared to controls, but did result in a significant decrease in active BMP1 and a resultant increase in Pro-BMP1, changes consistent with 7B2•PC2 mediated activation of BMP1 serving as the mechanism that regulates DMP1 degradation.