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Ryan C. Riddle, PhD

Department Affiliations Department of Orthopaedic Surgery
Rank Assistant Professor
Office Phone 410-502-6412
Lab Phone 410-287-6804
SOM Address 209 Ross

Meredith Zoch 2012 – 2016

Research Interests

Research in my laboratory is focused on Wnt/β-catenin signaling in musculoskeletal development and the role of bone in whole body metabolism. We utilize mouse genetics to examine receptor and intracellular signaling mechanisms and the communication of bone with other tissues. In one project, we are interested in the unique and overlapping functions of Wnt signaling components in the accrual of bone 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. We have generated transgenic mice lacking individual Frizzled receptors specifically in bone-forming osteoblasts to examine the requirement for these receptors during bone development and in the response to mechanical, hormonal, and other anabolic signals. In a second, but related project, we have found that mice lacking the Wnt co-receptor, low density lipoprotein-related receptor-5, in osteoblasts accumulate body fat and develop dyslipidemia. These findings led us to investigate the fuel requirements of osteoblasts during bone development and to examine how the skeleton communicates its metabolic needs with other tissues.


Research Profile

• Frey JL, Li Z, Ellis JM, Zhang Q, Farber CR, Aja S, Wolfgang MJ, Clemens TL, Riddle RC. 2015. Wnt-Lrp5 signaling regulates fatty acid metabolism in the osteoblast. Mol Cell Biol. 35:1979-1991. PMID 25802278

Riddle RC, Frey JL, Ferron M, Li Y, DiGirolamo DJ, Faugere MC, Hussain MA, Karsenty G, Clemens TL. 2014. Tsc2 is a molecular checkpoint controlling osteoblast development and glucose homeostasis. Mol Cell Biol. 34:1850-1862.PMID 24591652

Riddle RC, Diegel CR, Leslie JM, Van Koevering KK, Faugere MC, Clemens TL, Williams BO. 2013 Lrp5 and Lrp6 Exert Overlapping Functions in Osteoblasts During Postnatal Bone Acquisition. PLoS ONE 8(5): e63323. doi:10.1371/journal.pone.0063323. PMID 23675479

• Riddle RC, Leslie JM, Gross TS, Clemens TL. 2011. Hypoxia-inducible factor-1a protein negatively regulates load-induced bone formation. J Biol Chem. 286:44449-44456. PMID 22081627

• Mavalli MD, DiGirolamo DJ, Fan Y, Riddle RC, Campbell K, Sperling MA, van Groen T, Frank SJ, Bamman MM, Clemens TL. 2010. Differential Growth Hormone Receptor Signaling Modes Regulate Skeletal Muscle Development and Insulin Sensitivity. J Clin Invest. 120:4007-4020. PMID 20921627

• Fulzele K, Riddle RC, DiGirolamo DJ, Cao X, Wan C, Chen D, Faugere MC, Hussain MA, Brüning JC, Clemens TL. 2010. Insulin receptor signaling in osteoblasts regulates postnatal bone acquisition and body composition. Cell. 142:309-319. PMID 20655471