Session: OR31-Novel Signaling Mechanisms and Bone Cell Biology
W475 (McCormick Place West Building)
Outstanding Abstract Award
Methods: We used the ColI(2.3)+/Rs1+ transgenic mouse model where an engineered G-protein coupled receptor Rs1 activates Gs signaling in osteoblastic cells. We previously showed that these mice have 5-15 fold increases in trabecular bone formation resembling fibrous dysplasia of the bone. O2 consumption, CO2 production, movement, food, and water consumption were measured. Additionally, total body and bone marrow fat content were measured by EchoMRI, and blood was analyzed for glucose, insulin, and triacylglyceride levels after fasting. qPCR on whole bone was used to determine mRNA levels of genes involved in adipogenesis and osteoblast development. Seahorse metabolic stress tests were used to characterize the respiration capacity of bone marrow cells from control and ColI(2.3)+/Rs1+ mice.
Results: We found an unexpected 15% loss of total body fat and a 90% loss in tibial fat, as well as a 73% loss of blood triglyceride levels. Furthermore, ColI(2.3)+/Rs1+ mice showed decreased movement, food, and water consumption without alterations to energy expenditure. Seahorse mitochondrial stress test analysis on ColI(2.3)+/Rs1+ hematopoietic cells revealed a 50% decrease in basal respiration. qPCR indicated a decrease in genes expressed by mature adipocytes including Adiponectin and PRDM16. We also found increased levels of Wnt expression in ColI(2.3)+/Rs1+ bones.
Conclusions: ColI(2.3)+/Rs1+ mice show increased bone formation but decreased marrow adiposity, in contrast to other conditions of decreased bone formation and increased marrow adiposity. In addition, the ColI(2.3)+/Rs1+ bones showed decreased expression of mature adipocyte markers, possibly caused by a non-cell autonomous mechanism from the Rs1-expressing osteoblasts. Our findings suggest that osteoblasts may influence the metabolic homeostasis of bone through both changes in bioenergetics and cellular differentiation.
Nothing to Disclose: CC, JV, ECH
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