Research in Dr. Riddle’s laboratory is focused on Wnt/b-catenin signaling in musculoskeletal development. He utilizes mouse genetics to examine receptor and intracellular signaling mechanisms. In one project, he is interested in the unique and overlapping functions of Wnt signaling components in the accrual of bone and muscle mass. The Wnt pathway consists of 10 highly related Frizzled receptors, two co-receptors, and several ligands that activate signaling, and human mutations that modify signaling efficacy are associated with both high and low bone mass phenotypes. Using transgenic mice lacking Wnt signaling components in bone or muscle cells, his research seeks to determine the requirement for this signaling pathway during bone and muscle development and in the response to mechanical, hormonal, and other anabolic signals. In a second, but related project, his laboratory has found that mice lacking the Wnt co-receptor, low density lipoprotein-related receptor-5, in osteoblasts accumulate body fat and develop dyslipidemia. These findings have led to new studies designed to examine the energetic requirements of bone cells and to determine how the skeleton communicates its metabolic needs to other tissues.
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Riddle RC, Clemens TL. Bone cell bioenergetics and skeletal energy homeostasis. Physiol Rev. 2017 April;97(2):667-698. doi: 10.1152/physrev.00022.2016. Review.
Ziegler SG, Ferreira CR, MacFarlane EG, Riddle RC, Tomlinson RE, Chew EY, Martin L, Ma CT, Sergienko E, Pinkerton AB, Millán JL, Gahl WA, Dietz HC. Ectopic calcification in pseudoxanthoma elasticum responds to inhibition of tissue-nonspecific alkaline phosphatase. Sci Transl Med. 2017 Jun 7;9(393). pii: eaal1669. doi: 10.1126/scitranslmed.aal1669.
Tomlinson RE, Li Z, Li Z, Minichiello L, Riddle RC, Venkatesan A, Clemens TL. NGF-TrkA signaling in sensory nerves is required for skeletal adaptation to mechanical loads in mice. Proc Natl Acad Sci U S A. 2017 May 2;114(18):E3632-E3641. doi: 10.1073/pnas.1701054114. Epub 2017 Apr 17.
Li Z, Frey JL, Wong GW, Faugere MC, Wolfgang MJ, Kim JK, Riddle RC, Clemens TL. Glucose Transporter-4 Facilitates Insulin-Stimulated Glucose Uptake in Osteoblasts. Endocrinology. 2016 Nov;157(11):4094-4103. Epub 2016 Sep 30.
Zoch ML, Abou DS, Clemens TL, Thorek DL, Riddle RC. In vivo radiometric analysis of glucose uptake and distribution in mouse bone. Bone Res. 2016 Apr 5;4:16004. doi: 10.1038/boneres.2016.4. eCollection 2016.