Dr. Clemens lab is studying the mechanisms of action of insulin, insulin-like growth factor and growth hormone in one and skeletal muscle. Mice and their cells with specific alterations in the components of these pathways have been created and are being used to identify the interplay between these growth factors. In a separate project, we are investigating the hypothesis that the osteoblast and osteocytes are positioned in bone to sense and respond to fluctuations in oxygen and nutrient supply and thereby play key roles in regulation of angiogenesis and blood flow bone is under normal physiological conditions, and in response to pathological signals. Osteoblast cell models and genetically altered mice are being used to study the role of hypoxia inducible factors during bone development and following skeletal injury. This information will then be used to generate new diagnostic and therapeutic modalities.
- 1. Wang Y, Wan C, Deng L, Liu X, Cao X, Gilbert SR, Bouxsein ML, Faguere M-C, Guldberg RE,Gerstenfeld LC, Haase VH, Johnson RS, Schipani E, Clemens TL. The hypoxia-inducible factor αpathway couples angiogenesis to osteogenesis during skeletal development. J Clin Invest2007;117:1616-1626, PMCID: PMC1878533.
- 2. Fulzele K, DiGirolamo DJ, Liu Z, Xu J, Messina JL, Clemens TL. Disruption of the IGF-1 Receptor in Osteoblasts Enhances Insulin Signaling and Action. J Biol Chem 2007;282:25649-25658, PMID:17553792.
- 3. DiGirolamo DJ, Mukherjee A; Fulzele K; Gan Y; Cao X; Frank SJ; Clemens TL. Mode of Growth Hormone Action in Osteoblasts. J Biol Chem 2007;282:31666-74, PMID: 17698843.
- 4. Wan C, Gilbert SR, Wang Y, Cao X, Shen X, Ramaswamy G, Jacobsen KA, Alaql ZS, Eberhardt AW,Gerstenfeld LC, Einhorn TA, Deng L, Clemens TL. Activation of the hypoxia inducible factor-1αpathway accelerates bone regeneration. Proc Nat’l Acad Sci USA 2008;105:686-691, PMID: 18184809.
- 5. Mak KK, Bi Y, Wan C, Chuang P-T, Clemens T, Young M and Yang Y. Hedgehog signaling in matureosteoblasts regulates bone formation and resorption by controlling PTHrP and RANKL expression. DevCell. 2008 May;14(5):674-88, PMID: 18477451. 23 2/2/10
- 6. Tang Y Liu Z, Zhao L, Wu D, Clemens T and Cao X. Smad7 Stabilizes β-catenin Binding to E-cadherinComplex and Promotes Cell-Cell adhesion. J Biol Chem 2008;283:23956-3963, PMID: 18593713.
- 7. Riddle RC, Khatri R, Schipani E, Clemens TL. Role of Hypoxia-Inducible Factor-1α in Angiogenic-Osteogenic Coupling. J Mol Med 2009 87:583-90.