Fig. 7: Inhibition of DDAH1 by PD404182 reduces bone formation but administration of AAV-DDAH1 accelerates bone healing in vivo. | Nature Communications

Fig. 7: Inhibition of DDAH1 by PD404182 reduces bone formation but administration of AAV-DDAH1 accelerates bone healing in vivo.

From: Mechanical force promotes dimethylarginine dimethylaminohydrolase 1-mediated hydrolysis of the metabolite asymmetric dimethylarginine to enhance bone formation

Fig. 7

a Schematic illustration of in vivo treatment model. b Representative micro-CT images of trabecular bone in the distal femur (left) of ground and unload treatment mice administrated by vehicle or PD404182. c–f Bone mineral density (BMD), Bone volume/total volume (BV/TV), trabecular bone thickness (Tb.Th) and trabecular bone number (Tb.N) of Ddah1+/+ and Ddah1−/− mice in the administration of vehicle or PD404182. Ddah1+/+ vehicle-treated, n = 5. Ddah1+/+ PD404182-treated, n = 5. Ddah1−/− vehicle-treated, n = 5. Ddah1−/− PD404182-treated, n = 5. *p < 0.05. **p < 0.01. ***p < 0.005. Data are represented as mean values ± SD. g Representative immunofluorescence staining images of trabecular bone in Ddah1+/+ and Ddah1−/− mice in the administration of vehicle or PD404182. Scale bar = 100 μm. Yellow arrows for OCN positive cells. h Representative calcein labeling images of trabecular bone in Ddah1+/+ and Ddah1−/− mice in the administration of vehicle or PD404182. Scale bar = 100 μm. i, j Quantification of the BFR/BS ratio and MAR. Ddah1+/+ vehicle-treated, n = 5. Ddah1+/+ PD404182-treated, n = 5. Ddah1−/− vehicle-treated, n = 5. Ddah1−/− PD404182-treated, n = 5. *p < 0.05. **p < 0.01. Data are represented as mean values ± SD. k Quantification of the OCN positive cells in bone parameters. Ddah1+/+ vehicle-treated, n = 5. Ddah1+/+ PD404182-treated, n = 5. Ddah1−/− vehicle-treated, n = 5. Ddah1−/− PD404182-treated, n = 5. *p < 0.05. ***p < 0.005. Data are represented as mean values ± SD. l Alteration of serum ADMA levels in Ddah1+/+ and Ddah1−/− mice in the administration of vehicle or PD404182 determined by LC-MS assay. Ddah1+/+ vehicle-treated, n = 5. Ddah1+/+ PD404182-treated, n = 5. Ddah1−/− vehicle-treated, n = 5. Ddah1−/− PD404182-treated, n = 5. **p < 0.01. ***p < 0.005. Data are represented as mean values ± SD. m Representative micro-CT images of bone defect from femur (left) of Ddah1f/f and Ddah1prx1 mice administrated by AAV-Zsgreen or AAV-DDAH1. n Bone mineral density (BMD) and bone volume/total volume (BV/TV) of bone healing in different groups of mice. Ddah1f/f AAV-Zsgreen-treated, n = 5. Ddah1prx1 AAV-Zsgreen-treated, n = 5. Ddah1prx1 AAV-DDAH1-treated, n = 5. *p < 0.05. **p < 0.01. Data are represented as mean values ± SD. The data were analyzed by one-way analysis of variance (ANOVA) with post-hoc Tukey’s test.

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