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Matthew J. Hilton

Associate Professor in Orthopaedic Surgery and Cell Biology
(919) 613-9761
Research Interest: 
Developmental biology
Genetics
Signal transduction
Research Summary: 
Cellular and molecular mechanisms that regulate skeletal development, disease, and repair or regeneration.
Research Description: 

A long-term interest of the Hilton laboratory is to uncover the molecular circuitry regulating lineage commitment, proliferation, and differentiation of skeletal stem cells, cartilage cells (chondrocytes), and bone cells (osteoblasts). My lab uses genetic and surgical mouse models as well as primary cell culture techniques coupled with cell and molecular biology to answer questions regarding skeletal stem cell self-renewal and differentiation, chondrogenesis, and osteoblastogenesis. Our research focus is divided into three overlapping research programs that include: Skeletal Development, Skeletal Disease, and Skeletal Repair and Regeneration.

Skeletal Development

A multitude of cell signaling pathways are required throughout skeletal development. Deregulation of these signaling cicuits causes a variety of skeletal dysplasias.  Recently, we identified the Notch signaling pathway as important regulator of skeletal development.  We are currently employing mouse genetic and primary cell culture techniques to understand the cell and molecular mechanisms by which Notch, and other related signaling pathways, coordinate and control skeletal development. Through our understanding of skeletal development we have generated several complex genetic mouse models of congenital skeletal disorders.

Skeletal Disease

Osteoarthritis (OA) is one of the most common, debilitating, and expensive diseases that affect the skeleton.  OA is characterized by joint cartilage and mensicus degeneration, subchondral bone sclerosis, synovial hyperplasia, and chondrophyte/osteophyte formation. Our laboratory has a particular interest in the genetics that underlie the normal maintenance and the pathological degeneration of synovial joint tissues observed in the context of OA. We employ both genetic and surgical mouse models to follow the cellular and molecular changes associated with OA and are currently exploring the role that the Notch signaling pathway plays in maintaining joint homeostasis.

Skeletal Repair and Regeneration

Skeletal injuries, such as bone fractures or critical sized bone defects, repair or attempt to repair through mechanisms that are very similar to the processes involved in skeletal development. Our laboratory is interested in uncovering the role that various signaling pathways play during skeletal repair or regeneration. We are using genetic, surgical, and skeletal stem cell based approaches at understanding the processes inolved in skeletal repair, as well as, developing novel techniques and approaches for enhancing or accelerating skeletal regeneration. Our lab is particularly interested in the most complex skeletal repair situations that often result in fracture non-union.

Publications: 
Transient gamma-secretase inhibition accelerates and enhances fracture repair likely via Notch signaling modulation.
Wang C, Shen J, Yukata K, Inzana JA, O'Keefe RJ, Awad HA, Hilton MJ.
Bone. 2015. 73:77-89.

NOTCH-Mediated Maintenance and Expansion of Human Bone Marrow Stromal/Stem Cells: A Technology Designed for Orthopedic Regenerative Medicine.
Dong Y, Long T, Wang C, Mirando AJ, Chen J, O'Keefe RJ, Hilton MJ.
Stem Cells Transl Med. 2014. 3:1456-66.

RBP-Jκ-dependent Notch signaling is required for murine articular cartilage and joint maintenance.
Mirando AJ, Liu Z, Moore T, Lang A, Kohn A, Osinski AM, O'Keefe RJ, Mooney RA, Zuscik MJ, Hilton MJ.
Arthritis Rheum. 2013. 65:2623-33.

Cartilage-specific RBPjκ-dependent and -independent Notch signals regulate cartilage and bone development.
Kohn A, Dong Y, Mirando AJ, Jesse AM, Honjo T, Zuscik MJ, O'Keefe RJ, Hilton MJ.
Development. 2012. 139:1198-212.

RBPjkappa-dependent Notch signaling regulates mesenchymal progenitor cell proliferation and differentiation during skeletal development.
Dong Y, Jesse AM, Kohn A, Gunnell LM, Honjo T, Zuscik MJ, O'Keefe RJ, Hilton MJ.
Development. 2010. 137:1461-71.