Fig. 8: Adenylyl cyclase inhibition blocks Ddr2Adipo bone phenotypes.
From: Targeting adipocytic discoidin domain receptor 2 impedes fat gain while increasing bone mass
A Quantitative μCT analysis of femurs of Ddr2Adipo mice treated with or without Adenylyl cyclase inhibitor SQ22536. n = 6 femurs from 6 mice for each group. Data are presented as mean ± SEM. *P < 0.05; **P < 0.01 as determined by unpaired t-test. B Schematic overview of bone-fat crosstalk mediated by Ddr2. In bone marrow microenvironment, bone marrow adipocytes modulate osteoblasts. In WT mice, the expression level of Adcy5 is low, due to inhibition by Ddr2. The cAMP-PKA signaling remains in an inactive status. In Ddr2Adipo mice, expression of Adcy5 is increased, leading to stimulated cAMP-PKA pathway and subsequent increased lipolysis and fatty acid release. Uptake of fatty acid by nearby osteoblasts stimulates the mitochondrial OXPHOS and provides more energy for osteoblast differentiation and bone formation. BMA bone marrow adipocyte, OB osteoblast, cAMP cyclic adenosine monophosphate, PKA protein kinase A.
