The CORT Program was initiated in 2006 and has had a transformative impact on the musculoskeletal research program at the University of Rochester. The Program has focused the collective efforts of an experienced, talented, and multi-disciplinary research team. The objective of the CORT Program is to translate understanding of the molecular, cellular and tissues responses involved in musculoskeletal injury into novel therapies for tissue regeneration and repair. The scientific basis of the CORT program is that injury and repair responses are fundamentally dependent upon the ability of stem cell progenitors to undergo proliferation and expansion, and subsequent tissue specific differentiation. The unifying theme of the CORT Program is that PTH is a key anabolic agent that promotes tissue-specific MSC expansion and repair events. The CORT renewal application continues a Program designed to transform the treatments of two major musculoskeletal diseases, 1) skeletal injury and 2) joint injury/osteoarthritis. Both diseases have a higher incidence and greater affect on the elderly. The CORT program has stimulated scientific discoveries resulting in the generation of 61 manuscripts. Project 1, "Teriparatide as a Therapy for Osteoarthritis Following Meniscal Injury" uses in vivo and in vitro preclinical models and human tissues and cells to define the mechanism involved in the chondro-protective effect of PTH on articular cartilage. Project 2, "Role of PTH in Enhancing Fracture Repair in Aging" defines the downstream signals and targets that PTH activates and which are necessary for the stimulation of bone repair. Project 3: "Translating PTH Therapy as an Adjuvant for Structural Allografting" expands the translational scope of the CORT by examining the therapeutic potential of PTH in bone repair in a canine model and includes a human clinical pilot study. The projects are supported by an Administrative Core that enhances collaborations and integration with the institutional CTSI and research base, and an innovative and comprehensive Molecular and Anatomic Imaging Core. The Program has the entire constellation of factors necessary for success, including: i) a collaborative research team;ii) an exceptional research infrastructure that permits comprehensive experimental approaches;iii) a history of scientific innovation and commitment to translational research;iv) excellent integration of and access to institutional research resources and facilities by a talented research team.

Public Health Relevance

The goal of the CORT Program is to translate the scientific principle that PTH is a key anabolic agent that promotes tissue-specific MSC expansion and repair events into effective therapies for the treatment of patients with traumatic injuries of the bones and joints.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Specialized Center (P50)
Project #
5P50AR054041-07
Application #
8531854
Study Section
Special Emphasis Panel (ZAR1-KM (M1))
Program Officer
Panagis, James S
Project Start
2006-08-15
Project End
2017-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
7
Fiscal Year
2013
Total Cost
$1,386,713
Indirect Cost
$478,347
Name
University of Rochester
Department
Orthopedics
Type
Schools of Dentistry
DUNS #
041294109
City
Rochester
State
NY
Country
United States
Zip Code
14627
Hamada, Daisuke; Maynard, Robert; Schott, Eric et al. (2016) Suppressive Effects of Insulin on Tumor Necrosis Factor-Dependent Early Osteoarthritic Changes Associated With Obesity and Type 2 Diabetes Mellitus. Arthritis Rheumatol 68:1392-402
Liu, Z; Ren, Y; Mirando, A J et al. (2016) Notch signaling in postnatal joint chondrocytes, but not subchondral osteoblasts, is required for articular cartilage and joint maintenance. Osteoarthritis Cartilage 24:740-51
Zhang, Yongchun; Sheu, Tzong-jen; Hoak, Donna et al. (2016) CCN1 Regulates Chondrocyte Maturation and Cartilage Development. J Bone Miner Res 31:549-59
Sheyn, Dmitriy; Shapiro, Galina; Tawackoli, Wafa et al. (2016) PTH Induces Systemically Administered Mesenchymal Stem Cells to Migrate to and Regenerate Spine Injuries. Mol Ther 24:318-30
Papuga, Mark O; Mesfin, Addisu; Molinari, Robert et al. (2016) Correlation of PROMIS Physical Function and Pain CAT Instruments With Oswestry Disability Index and Neck Disability Index in Spine Patients. Spine (Phila Pa 1976) 41:1153-9
de Mesy Bentley, Karen L; Trombetta, Ryan; Nishitani, Kohei et al. (2016) Evidence of Staphylococcus aureus Deformation, Proliferation and Migration in Canaliculi of Live Cortical Bone in Murine Models of Osteomyelitis. J Bone Miner Res :
Han, Songfeng; Proctor, Ashley R; Vella, Joseph B et al. (2016) Non-invasive diffuse correlation tomography reveals spatial and temporal blood flow differences in murine bone grafting approaches. Biomed Opt Express 7:3262-3279
Wang, Cuicui; Inzana, Jason A; Mirando, Anthony J et al. (2016) NOTCH signaling in skeletal progenitors is critical for fracture repair. J Clin Invest 126:1471-81
Zhang, Hengwei; Sun, Wen; Li, Xing et al. (2016) Use of Hes1-GFP reporter mice to assess activity of the Hes1 promoter in bone cells under chronic inflammation. Bone 90:80-9
Antebi, Ben; Zhang, Longze; Sheyn, Dmitriy et al. (2016) Controlling Arteriogenesis and Mast Cells Are Central to Bioengineering Solutions for Critical Bone Defect Repair Using Allografts. Bioengineering (Basel) 3:

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