Hilton Lab
Matthew J. Hilton
Ph.D. 2004 University of Houston
Assistant Professor of Orthopaedics,
Center for Musculoskeletal Research
Contact:
Matthew J. Hilton, Ph.D.
University of Rochester Medical Center
601 Elmwood Ave., Box 665
Rochester, NY 14642
Office: SMD 1-8535
(585) 275-1335
matthew_hilton@urmc.rochester.edu
Research Overview
Most of the bones in the vertebrate skeleton arise from a cartilage template during embryogenesis. This process, known as endochondral ossification, begins with the differentiation of condensed mesenchymal stem cells (MSCs) into chondroprogenitors (immature cartilage cells) and osteoprogenitors (immature bone cells). Both the chondroprogenitor and osteoprogenitor cells undergo a coupled proliferation and differentiation program ultimately leading to the formation of mature cartilage and bone. Various genetic studies have demonstrated that Ihh, Pthrp, BMPs, FGFs, and canonical Wnt signaling pathways are required at multiple stages of normal cartilage and bone development. Deregulation of these signaling circuits during development are a primary cause for a variety of skeletal dysplasias, as well as, age related cartilage and bone pathologies.
A long-term interest of the Hilton lab is to uncover the molecular circuitry regulating lineage commitment, proliferation, and differentiation of MSCs and maturing chondrocytes. My laboratory uses genetic mouse models and primary cell culture techniques coupled with biochemistry to answer questions regarding MSC self-renewal/differentiation, chondrogenesis, and chondrocyte maturation. Recently my lab has generated novel data from a variety of Notch gain and loss-of-function mutant mice demonstrating that Notch suppresses MSC differentiation and plays critical roles in regulating chondrogenesis and chondrocyte maturation. We are currently investigating the exact Notch signaling mechanisms regulating both early and late stages of these processes, as well as, determining how Notch components interact with other known signaling pathways during cartilage development and maintenance. These studies are also being extended to aid in our mechanistic understanding of both fracture repair and osteoarthritis.
Projects
Recent Selected Publications
Hilton MJ, Tu X, Bai S, Zhao H, Kobayashi T, Kronenberg HM, Teitelbaum SL, Ross FP, Kopan R, and Long F. (2008). Notch Signaling Maintains Bone Marrow Mesenchymal Progenitors by Suppressing Osteoblast Differentiation. Nature Medicine, 14 (3): 306-14.
Zuscik M, Hilton MJ, Zhang X, Chen D, and O’Keefe RJ. (2008). Regulation of Chondrogenesis and Chondrocyte Differentiation by Stress. Journal of Clinical Investigation, 118(2): 429-38.
Hilton MJ, Tu X, and Long F. (2007). Gene Deletion Using a Tamoxifen-inducible Col2-CreTM Transgenic Mouse Reveals Expression of Cola1(II)A Splice Form by Trabecular Osteoblastic Cells, and Direct Regulation of PTHrP Expression and Chondrocyte Morphology by Ihh. Developmental Biology, 308 (1): 93-105.
Hilton MJ, Tu X, Cook J, Hu H, and Long F. (2005). Ihh Controls Cartilage Development by Antagonizing Gli3 but Requires Additional Effectors to Regulate Osteoblast and Vascular Development. Development, 132(19):4339-51.
Hu H, Hilton MJ, Tu X, Yu K, Ornitz DM, and Long F. (2005). Sequential Roles of Hedgehog and Wnt Signaling in Osteoblast Development. Development, 132(1): 49-60.
Hilton MJ, Gutierrez L, Martinez D, and Wells DE. (2005). EXT1 Regulates Chondroctye Proliferation and Differentiation During Endochondral Bone Development. Bone, 36(3): 379-86.
More papers: 
