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)
Type
Specialized Center (P50)
Project #
3P50AR054041-08S2
Application #
8893754
Study Section
Special Emphasis Panel (ZAR1)
Program Officer
Panagis, James S
Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Rochester
Department
Orthopedics
Type
School of Medicine & Dentistry
DUNS #
City
Rochester
State
NY
Country
United States
Zip Code
14627
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Zhang, Minjie; Feigenson, Marina; Sheu, Tzong-jen et al. (2015) Loss of the PGE2 receptor EP1 enhances bone acquisition, which protects against age and ovariectomy-induced impairments in bone strength. Bone 72:92-100
David, Michael A; Jones, Khyrie H; Inzana, Jason A et al. (2014) Tendon repair is compromised in a high fat diet-induced mouse model of obesity and type 2 diabetes. PLoS One 9:e91234
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Shi, Jixiang; Liang, Qianqian; Zuscik, Michael et al. (2014) Distribution and alteration of lymphatic vessels in knee joints of normal and osteoarthritic mice. Arthritis Rheumatol 66:657-66
Varrone, John J; de Mesy Bentley, Karen L; Bello-Irizarry, Sheila N et al. (2014) Passive immunization with anti-glucosaminidase monoclonal antibodies protects mice from implant-associated osteomyelitis by mediating opsonophagocytosis of Staphylococcus aureus megaclusters. J Orthop Res 32:1389-96
Jonason, Jennifer H; O'Keefe, Regis J (2014) Isolation and culture of neonatal mouse calvarial osteoblasts. Methods Mol Biol 1130:295-305
Nishitani, Kohei; Schwarz, Edward M (2014) Regenerative medicine: Cartilage transplants hold promise for challenging bone defects. Nat Rev Rheumatol 10:129-30
Li, T-F; Yukata, K; Yin, G et al. (2014) BMP-2 induces ATF4 phosphorylation in chondrocytes through a COX-2/PGE2 dependent signaling pathway. Osteoarthritis Cartilage 22:481-9
Yin, Guoyong; Sheu, Tzong-Jen; Menon, Prashanthi et al. (2014) Impaired angiogenesis during fracture healing in GPCR kinase 2 interacting protein-1 (GIT1) knock out mice. PLoS One 9:e89127

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