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 #
3P50AR054041-08S1
Application #
8864466
Study Section
Special Emphasis Panel (ZAR1)
Program Officer
Panagis, James S
Project Start
2006-08-15
Project End
2015-07-31
Budget Start
2014-08-01
Budget End
2015-07-31
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
Zhang, Longze; Wang, Tao; Chang, Martin et al. (2017) Teriparatide Treatment Improves Bone Defect Healing Via Anabolic Effects on New Bone Formation and Non-Anabolic Effects on Inhibition of Mast Cells in a Murine Cranial Window Model. J Bone Miner Res 32:1870-1883
Zhang, Yongchun; O'Keefe, Regis J; Jonason, Jennifer H (2017) BMP-TAK1 (MAP3K7) Induces Adipocyte Differentiation Through PPAR? Signaling. J Cell Biochem 118:204-210
Schwarz, Edward M (2017) Confirmation of Sexual Dimorphisms in Metal Hypersensitivity and Joint Pain Following Total Joint Arthroplasty: Commentary on an article by Marco S. Caicedo, PhD, et al.: ""Females with Unexplained Joint Pain Following Total Joint Arthroplasty Exhibit a H J Bone Joint Surg Am 99:e41
Wang, Wensheng; Wang, Hua; Zhou, Xichao et al. (2017) Lymphatic Endothelial Cells Produce M-CSF, Causing Massive Bone Loss in Mice. J Bone Miner Res 32:939-950
Sun, Wen; Zhang, Hengwei; Wang, Hua et al. (2017) Targeting Notch-Activated M1 Macrophages Attenuates Joint Tissue Damage in a Mouse Model of Inflammatory Arthritis. J Bone Miner Res 32:1469-1480
Le Bleu, Heather K; Kamal, Fadia A; Kelly, Meghan et al. (2017) Extraction of high-quality RNA from human articular cartilage. Anal Biochem 518:134-138
Nishitani, Kohei; Mietus, Zachary; Beck, Christopher A et al. (2017) High dose teriparatide (rPTH1-34) therapy increases callus volume and enhances radiographic healing at 8-weeks in a massive canine femoral allograft model. PLoS One 12:e0185446
Feigenson, Marina; Eliseev, Roman A; Jonason, Jennifer H et al. (2017) PGE2 Receptor Subtype 1 (EP1) Regulates Mesenchymal Stromal Cell Osteogenic Differentiation by Modulating Cellular Energy Metabolism. J Cell Biochem 118:4383-4393
Lawal, Rialnat A; Zhou, Xichao; Batey, Kaylind et al. (2017) The Notch Ligand Jagged1 Regulates the Osteoblastic Lineage by Maintaining the Osteoprogenitor Pool. J Bone Miner Res 32:1320-1331
de Mesy Bentley, Karen L; Trombetta, Ryan; Nishitani, Kohei et al. (2017) Evidence of Staphylococcus Aureus Deformation, Proliferation, and Migration in Canaliculi of Live Cortical Bone in Murine Models of Osteomyelitis. J Bone Miner Res 32:985-990

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