REGIS J O'KEEFE

Summary

Affiliation: University of Rochester
Country: USA

Publications

  1. ncbi Bone tissue engineering and regeneration: from discovery to the clinic--an overview
    REGIS J O'KEEFE
    Department of Orthopaedic Surgery, Center for Musculoskeletal Research, University of Rochester, Rochester, New York 14642, USA
    Tissue Eng Part B Rev 17:389-92. 2011
  2. ncbi Smad6 is induced by BMP-2 and modulates chondrocyte differentiation
    Xeufeng Li
    Center for Musculoskeletal Research, Department of Orthopaedics, University of Rochester Medical Center, 601 Elmwood Avenue, Box 665, Rochester, NY 14642, USA
    J Orthop Res 21:908-13. 2003
  3. ncbi COX-2 has a critical role during incorporation of structural bone allografts
    REGIS J O'KEEFE
    Department of Orthopedics, The Center for Musculoskeletal Research, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA
    Ann N Y Acad Sci 1068:532-42. 2006
  4. ncbi Inhibition of beta-catenin signaling causes defects in postnatal cartilage development
    Mo Chen
    Department of Orthopaedics, Center for Musculoskeletal Research, University of Rochester School of Medicine, Rochester, NY 14642, USA
    J Cell Sci 121:1455-65. 2008
  5. ncbi Cartilage-specific RBPjκ-dependent and -independent Notch signals regulate cartilage and bone development
    Anat Kohn
    Department of Orthopaedics and Rehabilitation, Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY 14642, USA
    Development 139:1198-212. 2012
  6. ncbi EP1(-/-) mice have enhanced osteoblast differentiation and accelerated fracture repair
    Minjie Zhang
    Center for Musculoskeletal Research, University of Rochester, Rochester, NY, USA
    J Bone Miner Res 26:792-802. 2011
  7. ncbi Periosteal progenitor cell fate in segmental cortical bone graft transplantations: implications for functional tissue engineering
    Xinping Zhang
    Department of Orthopaedics, University of Rochester Medical Center, New York, USA
    J Bone Miner Res 20:2124-37. 2005
  8. ncbi Parathyroid hormone-related peptide (PTHrP) inhibits Runx2 expression through the PKA signaling pathway
    Tian Fang Li
    Department of Orthopaedics, The Center for Musculoskeletal Research, University of Rochester, Rochester, NY 14642, USA
    Exp Cell Res 299:128-36. 2004
  9. ncbi Runx1/AML1/Cbfa2 mediates onset of mesenchymal cell differentiation toward chondrogenesis
    Yongjun Wang
    Center for Musculoskeletal Research, Department of Orthopeadics, University of Rochester, Rochester, New York 14642, USA
    J Bone Miner Res 20:1624-36. 2005
  10. ncbi PGE2 signaling through the EP4 receptor on fibroblasts upregulates RANKL and stimulates osteolysis
    Ryosuke Tsutsumi
    Center for Musculoskeletal Research, University of Rochester, Rochester, New York, USA
    J Bone Miner Res 24:1753-62. 2009

Research Grants

  1. Cyclooxygenases in Skeletal Repair
    REGIS O KEEFE; Fiscal Year: 2007
  2. Training in Orthopaedic Research
    REGIS O KEEFE; Fiscal Year: 2007
  3. Prostaglandin Signaling in Wear Debris-induced Osteolysis
    REGIS O KEEFE; Fiscal Year: 2007
  4. The use of genetic models to define the role of beta-catenin in post-natal growth
    REGIS O KEEFE; Fiscal Year: 2007
  5. Prostaglandin Signaling in Wear Debris-induced Osteolysis
    REGIS O KEEFE; Fiscal Year: 2009
  6. The use of genetic models to define the role of beta-catenin in post-natal growth
    REGIS O KEEFE; Fiscal Year: 2009
  7. Cyclooxygenases in Skeletal Repair
    REGIS O KEEFE; Fiscal Year: 2009
  8. Cyclooxygenases in Skeletal Repair
    Xinping Zhang; Fiscal Year: 2010
  9. GROWTH FACTORS AND EPIPHYSEAL CHONDROCYTE MATURATION
    REGIS O KEEFE; Fiscal Year: 2006
  10. GROWTH FACTORS AND EPIPHYSEAL CHONDROCYTE MATURATION
    REGIS O KEEFE; Fiscal Year: 2001

Collaborators

Detail Information

Publications84

  1. ncbi Bone tissue engineering and regeneration: from discovery to the clinic--an overview
    REGIS J O'KEEFE
    Department of Orthopaedic Surgery, Center for Musculoskeletal Research, University of Rochester, Rochester, New York 14642, USA
    Tissue Eng Part B Rev 17:389-92. 2011
    ..Collectively, manuscripts in this volume provide luminary examples toward identification of barriers and strategies for translation of fundamental discoveries into clinical therapeutics...
  2. ncbi Smad6 is induced by BMP-2 and modulates chondrocyte differentiation
    Xeufeng Li
    Center for Musculoskeletal Research, Department of Orthopaedics, University of Rochester Medical Center, 601 Elmwood Avenue, Box 665, Rochester, NY 14642, USA
    J Orthop Res 21:908-13. 2003
    ..Additional studies are required to determine the extent to which this pathway participates in pathologic processes involving cartilage...
  3. ncbi COX-2 has a critical role during incorporation of structural bone allografts
    REGIS J O'KEEFE
    Department of Orthopedics, The Center for Musculoskeletal Research, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA
    Ann N Y Acad Sci 1068:532-42. 2006
    ..Furthermore, our data support the notion that COX-2-dependent PGE2 produced at the early stage of bone healing is prerequisite for efficient skeletal repair...
  4. ncbi Inhibition of beta-catenin signaling causes defects in postnatal cartilage development
    Mo Chen
    Department of Orthopaedics, Center for Musculoskeletal Research, University of Rochester School of Medicine, Rochester, NY 14642, USA
    J Cell Sci 121:1455-65. 2008
    ..Altogether the findings confirm a crucial role for Wnt/beta-catenin in postnatal growth...
  5. ncbi Cartilage-specific RBPjκ-dependent and -independent Notch signals regulate cartilage and bone development
    Anat Kohn
    Department of Orthopaedics and Rehabilitation, Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY 14642, USA
    Development 139:1198-212. 2012
    ..Finally, cartilage-specific RBPjκ-independent Notch signaling likely regulates Ihh responsiveness during cartilage and bone development...
  6. ncbi EP1(-/-) mice have enhanced osteoblast differentiation and accelerated fracture repair
    Minjie Zhang
    Center for Musculoskeletal Research, University of Rochester, Rochester, NY, USA
    J Bone Miner Res 26:792-802. 2011
    ..We show that unlike the PGE(2) receptors EP2 and EP4, the EP1 receptor is a negative regulator that acts at multiple stages of the fracture healing process. Inhibition of EP1 signaling is a potential means to enhance fracture healing...
  7. ncbi Periosteal progenitor cell fate in segmental cortical bone graft transplantations: implications for functional tissue engineering
    Xinping Zhang
    Department of Orthopaedics, University of Rochester Medical Center, New York, USA
    J Bone Miner Res 20:2124-37. 2005
    ....
  8. ncbi Parathyroid hormone-related peptide (PTHrP) inhibits Runx2 expression through the PKA signaling pathway
    Tian Fang Li
    Department of Orthopaedics, The Center for Musculoskeletal Research, University of Rochester, Rochester, NY 14642, USA
    Exp Cell Res 299:128-36. 2004
    ..Overall, our results demonstrate that PTHrP downregulates Runx2 expression primarily through the PKA signaling pathway...
  9. ncbi Runx1/AML1/Cbfa2 mediates onset of mesenchymal cell differentiation toward chondrogenesis
    Yongjun Wang
    Center for Musculoskeletal Research, Department of Orthopeadics, University of Rochester, Rochester, New York 14642, USA
    J Bone Miner Res 20:1624-36. 2005
    ..Runx1 induces mesenchymal stem cell commitment to the early stages of chondrogenesis...
  10. ncbi PGE2 signaling through the EP4 receptor on fibroblasts upregulates RANKL and stimulates osteolysis
    Ryosuke Tsutsumi
    Center for Musculoskeletal Research, University of Rochester, Rochester, New York, USA
    J Bone Miner Res 24:1753-62. 2009
    ..These results show that periprosthetic fibroblasts are important mediators of osteolysis through the expression of RANKL, which is induced after PGE2 signaling through the EP4 receptor...
  11. ncbi Wnt induction of chondrocyte hypertrophy through the Runx2 transcription factor
    Yu Feng Dong
    Center for Musculoskeletal Research, University of Rochester, Rochester, New York, USA
    J Cell Physiol 208:77-86. 2006
    ....
  12. ncbi Activation of beta-catenin signaling in articular chondrocytes leads to osteoarthritis-like phenotype in adult beta-catenin conditional activation mice
    Mei Zhu
    Department of Orthopaedics, Center for Musculoskeletal Research, University of Rochester School of Medicine, Rochester, New York 14642, USA
    J Bone Miner Res 24:12-21. 2009
    ..This study provides direct and definitive evidence about the role of beta-catenin in the development of OA...
  13. ncbi Axin2 regulates chondrocyte maturation and axial skeletal development
    Debbie Y Dao
    Department of Orthopaedics, Center for Musculoskeletal Research, University of Rochester School of Medicine, Rochester, New York 14642, USA
    J Orthop Res 28:89-95. 2010
    ..In the presence of a heterozygous deficiency of Axin1, Axin2 was also shown to play a critical role in craniofacial and axial skeleton development...
  14. ncbi Runx3/AML2/Cbfa3 regulates early and late chondrocyte differentiation
    Do Y Soung
    Center for Musculoskeletal Research, University of Rochester, Rochester, New York 14642, USA
    J Bone Miner Res 22:1260-70. 2007
    ..We found that Runx3 is essential for mediating the early stage of endochondral ossification through cooperation with other Runx family members...
  15. ncbi Reduction of particle-induced osteolysis by interleukin-6 involves anti-inflammatory effect and inhibition of early osteoclast precursor differentiation
    Michael Darowish
    Center for Musculoskeletal Research, University of Rochester, School of Medicine and Dentistry, Rochester, NY 14642, USA
    Bone 45:661-8. 2009
    ..Thus, the absence of IL-6 results in increased inflammatory bone loss...
  16. ncbi Reduced COX-2 expression in aged mice is associated with impaired fracture healing
    Amish A Naik
    The Center for Musculoskeletal Research, University of Rochester, Rochester, New York 14642, USA
    J Bone Miner Res 24:251-64. 2009
    ..The findings suggest that COX-2/EP4 agonists may compensate for deficient molecular signals that result in the reduced fracture healing associated with aging...
  17. ncbi Smurf2 induces degradation of GSK-3beta and upregulates beta-catenin in chondrocytes: a potential mechanism for Smurf2-induced degeneration of articular cartilage
    Qiuqian Wu
    Center for Musculoskeletal Research, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA
    Exp Cell Res 315:2386-98. 2009
    ....
  18. ncbi Teriparatide (1-34 human PTH) regulation of osterix during fracture repair
    Lee A Kaback
    The Center for Musculoskeletal Research, University of Rochester, Rochester, New York, USA
    J Cell Biochem 105:219-26. 2008
    ..Collectively, these data suggest a mechanism for teriparatide mediated fracture healing possibly via Osx induction in MSCs...
  19. ncbi Remodeling of murine intrasynovial tendon adhesions following injury: MMP and neotendon gene expression
    Alayna E Loiselle
    Department of Orthopaedics, The Center for Musculoskeletal Research, University of Rochester Box 665, 601 Elmwood Avenue, Rochester, New York 14620, USA
    J Orthop Res 27:833-40. 2009
    ..The murine model of primary tendon repair, described here, provides a novel mechanism to study the tendon healing process, and further enhances the understanding of this process at the molecular, cellular, and biomechanical level...
  20. ncbi Smad7 mediates inhibition of Saos2 osteosarcoma cell differentiation by NFkappaB
    Roman A Eliseev
    Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY 14642, USA
    Exp Cell Res 312:40-50. 2006
    ..We therefore conclude that in osteosarcoma Saos2 cells, NFkappaB represses BMP/Smad signaling and BMP2-induced differentiation through Smad7...
  21. ncbi Osterix/Sp7 regulates mesenchymal stem cell mediated endochondral ossification
    Lee A Kaback
    The Center for Musculoskeletal Research, University of Rochester, Rochester, New York, USA
    J Cell Physiol 214:173-82. 2008
    ....
  22. ncbi A phage display technique identifies a novel regulator of cell differentiation
    Tzong Jen Sheu
    Department of Orthopaedics, Center for Musculoskeletal Research, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA
    J Biol Chem 278:438-43. 2003
    ..We hypothesize that binding to TRAP may be one mechanism by which the full osteoblast phenotype is expressed during the process of bone remodeling...
  23. ncbi Induction of an osteoarthritis-like phenotype and degradation of phosphorylated Smad3 by Smurf2 in transgenic mice
    Qiuqian Wu
    Department of Orthopaedics, University of Rochester Medical Center, Rochester, New York 14642, USA
    Arthritis Rheum 58:3132-44. 2008
    ..To determine whether Smurf2, an E3 ubiquitin ligase known to inhibit transforming growth factor beta (TGFbeta) signaling, is expressed in human osteoarthritic (OA) cartilage and can initiate OA in mice...
  24. ncbi Ski inhibits TGF-β/phospho-Smad3 signaling and accelerates hypertrophic differentiation in chondrocytes
    Kyung Ok Kim
    Department of Orthopaedics and Rehabilitation, Center for Musculoskeletal Research, University of Rochester Medical Center, 601 Elmwood Avenue Box 665, Rochester, New York 14642, USA
    J Cell Biochem 113:2156-66. 2012
    ..These results suggest that inhibition of TGF-β signaling by Ski, which involves its association with phospho-Smad3 and recruitment of HDAC4 and 5, leads to accelerated chondrocyte differentiation...
  25. ncbi Teriparatide as a chondroregenerative therapy for injury-induced osteoarthritis
    Erik R Sampson
    Department of Orthopaedics and Rehabilitation, Center for Musculoskeletal Research, University of Rochester Medical Center, 601 Elmwood Avenue, Box 665, Rochester, NY 14642, USA
    Sci Transl Med 3:101ra93. 2011
    ..These preclinical findings provide proof of concept that Forteo may be useful for decelerating cartilage degeneration and inducing matrix regeneration in patients with osteoarthritis...
  26. ncbi Adhesions in a murine flexor tendon graft model: autograft versus allograft reconstruction
    Sys Hasslund
    The Center for Musculoskeletal Research, University of Rochester, Rochester, New York, USA
    J Orthop Res 26:824-33. 2008
    ..This mouse model can be useful in elucidating the molecular mechanisms in tendon repair and can aid in preliminary screening of molecular treatments of flexor tendon adhesions...
  27. ncbi ALK2 functions as a BMP type I receptor and induces Indian hedgehog in chondrocytes during skeletal development
    Donghui Zhang
    Center for Musculoskeletal Research, University of Rochester, Rochester, New York 14642, USA
    J Bone Miner Res 18:1593-604. 2003
    ..The findings suggest that BMP signaling modulates the Ihh/PTHrP signaling pathway that regulates the rate of chondrocyte differentiation...
  28. ncbi Parathyroid hormone-related peptide regulation of chick tibial growth plate chondrocyte maturation requires protein kinase A
    Michael J Zuscik
    Department of Orthopaedics, School of Medicine and Dentistry, University of Rochester, NY 14642, USA
    J Orthop Res 20:1079-90. 2002
    ..These data demonstrate that although activation of PKC or Ca2+ signals is not required, the cylic AMP-dependent A kinase is required for PTHrP to regulate key hallmarks of GPC phenotype...
  29. ncbi Transforming growth factor-beta stimulates cyclin D1 expression through activation of beta-catenin signaling in chondrocytes
    Tian Fang Li
    Department of Orthopaedics, Center for Musculoskeletal Research, University of Rochester, New York 14642, USA
    J Biol Chem 281:21296-304. 2006
    ..These results demonstrate that TGF-beta stimulates cyclin D(1) expression at least in part through activation of beta-catenin signaling...
  30. ncbi Inhibition of beta-catenin signaling in articular chondrocytes results in articular cartilage destruction
    Mei Zhu
    University of Rochester, Rochester, New York 14642, USA
    Arthritis Rheum 58:2053-64. 2008
    ..To determine the role of beta-catenin signaling in articular chondrocyte function, we generated Col2a1-ICAT-transgenic mice to inhibit beta-catenin signaling in chondrocytes...
  31. ncbi RBPjkappa-dependent Notch signaling regulates mesenchymal progenitor cell proliferation and differentiation during skeletal development
    Yufeng Dong
    Department of Orthopaedics and Rehabilitation, Center for Musculoskeletal Research, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA
    Development 137:1461-71. 2010
    ..Finally, Hes1 was identified as an RBPjkappa-dependent Notch target gene important for MPC maintenance and the suppression of in vitro chondrogenesis...
  32. ncbi Regulation of embryonic endochondral ossification by Smurf2
    Qiuqian Wu
    Department of Orthopaedics, Center for Musculoskeletal Research, University of Rochester Medical Center, 601 Elmwood Avenue, Box 665, Rochester, New York 14642, USA
    J Orthop Res 26:704-12. 2008
    ....
  33. ncbi Runx2/Cbfa1 stimulation by retinoic acid is potentiated by BMP2 signaling through interaction with Smad1 on the collagen X promoter in chondrocytes
    M Hicham Drissi
    The Center for Musculoskeletal Research, University of Rochester, Rochester, New York 14642, USA
    J Cell Biochem 90:1287-98. 2003
    ..Factors or signals that alter either of these transcription factors regulate the rate of chondrocyte differentiation...
  34. ncbi Prostaglandin E2 inhibits BMP signaling and delays chondrocyte maturation
    Christine A Clark
    Center for Musculoskeletal Research, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA
    J Orthop Res 27:785-92. 2009
    ..18 cells and in primary murine sternal chondrocytes. Altogether, the findings show that PGE2 regulates chondrocyte maturation in part by targeting BMP/Smad signaling and suggest an important role for PGE2 in endochondral bone formation...
  35. ncbi COX-2 from the injury milieu is critical for the initiation of periosteal progenitor cell mediated bone healing
    Chao Xie
    Center for Musculoskeletal Research, University of Rochester Medical Center, School of Medicine and Dentistry, 601 Elmwood Avenue, Rochester, NY 14642, USA
    Bone 43:1075-83. 2008
    ..Elimination of COX-2 at the early stage of healing could lead to detrimental effects on periosteal progenitor cell-initiated cortical bone repair...
  36. ncbi Cyclin D1-cdk4 induce runx2 ubiquitination and degradation
    Run Shen
    Department of Orthopaedics, Center for Musculoskeletal Research, University of Rochester School of Medicine, Rochester, NY 14642, USA
    J Biol Chem 281:16347-53. 2006
    ..The targeted Runx2 degradation by cyclin D1 identifies a novel mechanism through which Runx2 activity is regulated coordinately with the cell cycle machinery in bone cells...
  37. ncbi Overexpression of Smurf2 stimulates endochondral ossification through upregulation of beta-catenin
    Qiuqian Wu
    Department of Orthopaedics, Center for Musculoskeletal Research, University of Rochester Medical Center, 601 Elmwood Avenue, Box 665, Rochester, New York 14642, USA
    J Bone Miner Res 23:552-63. 2008
    ..The mechanism underlying Smurf2-mediated morphological changes during embryonic development may provide new mechanistic insights and potential targets for prevention and treatment of human osteoarthritis...
  38. ncbi 5-azacytidine alters TGF-beta and BMP signaling and induces maturation in articular chondrocytes
    Michael J Zuscik
    Center for Musculoskeletal Research, Department of Orthopaedics, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA
    J Cell Biochem 92:316-31. 2004
    ....
  39. ncbi Rescue of impaired fracture healing in COX-2-/- mice via activation of prostaglandin E2 receptor subtype 4
    Chao Xie
    The Center for Musculoskeletal Research, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA
    Am J Pathol 175:772-85. 2009
    ..Taken together, our studies demonstrate that EP2 and EP4 have differential functions during endochondral bone repair. Activation of EP4, but not EP2 rescued impaired bone fracture healing in COX-2(-/-) mice...
  40. ncbi Beta-catenin, cartilage, and osteoarthritis
    Qiuqian Wu
    Department of Orthopaedics and Rehabilitation, Center for Musculoskeletal Research, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA
    Ann N Y Acad Sci 1192:344-50. 2010
    ..These findings indicate that beta-catenin plays a central role in articular cartilage function and that activation of beta-catenin signaling may represent a pathologic mechanism for OA development...
  41. ncbi Bone marrow-derived matrix metalloproteinase-9 is associated with fibrous adhesion formation after murine flexor tendon injury
    Alayna E Loiselle
    Center for Musculoskeletal Research, University of Rochester, Rochester, New York, United States of America
    PLoS ONE 7:e40602. 2012
    ..These studies show that Mmp9 is primarily derived from bone marrow cells that migrate to the repair site, and mediates adhesion formation in injured tendons. Mmp9 is a potential target to limit adhesion formation in tendon healing...
  42. ncbi Effects of antiresorptive agents on osteomyelitis: novel insights into the pathogenesis of osteonecrosis of the jaw
    Dan Li
    The Center for Musculoskeletal Research, University of Rochester, Rochester, New York, USA
    Ann N Y Acad Sci 1192:84-94. 2010
    ....
  43. ncbi Aberrant hypertrophy in Smad3-deficient murine chondrocytes is rescued by restoring transforming growth factor beta-activated kinase 1/activating transcription factor 2 signaling: a potential clinical implication for osteoarthritis
    Tian Fang Li
    University of Rochester, Rochester, New York 14642, USA
    Arthritis Rheum 62:2359-69. 2010
    ....
  44. ncbi RANK signaling is not required for TNFalpha-mediated increase in CD11(hi) osteoclast precursors but is essential for mature osteoclast formation in TNFalpha-mediated inflammatory arthritis
    Ping Li
    Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York 14642, USA
    J Bone Miner Res 19:207-13. 2004
    ..RANK signaling is not required for the TNFalpha-stimulated increase in CD11b(hi) osteoclast precursors but is essential for mature osteoclast formation...
  45. ncbi Effects of receptor activator of NFkappaB (RANK) signaling blockade on fracture healing
    Lisa M Flick
    Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA
    J Orthop Res 21:676-84. 2003
    ..Together, these data imply that osteoclast depletion via inhibition of RANK signaling is a viable option for the treatment of pathological bone loss since no adverse effects on fracture healing are observed when therapy is discontinued...
  46. ncbi TAK1 regulates cartilage and joint development via the MAPK and BMP signaling pathways
    Lea M Gunnell
    Department of Orthopaedics and Rehabilitation, Center for Musculoskeletal Research, University of Rochester, Rochester, NY, USA
    J Bone Miner Res 25:1784-97. 2010
    ..Taken together, these data demonstrate that TAK1 is a critical regulator of both MAPK and BMP signaling and is necessary for proper cartilage and joint development...
  47. ncbi Autoimmunity and bone
    Edward M Schwarz
    Department of Orthopaedics, University of Rochester Medical Center, 601 Elmwood Avenue, Box 665, Rochester, NY 14642, USA
    Ann N Y Acad Sci 1068:275-83. 2006
    ..Thus, systemic factors produced by autoimmunity have a dramatic impact on active myelopoiesis and bone homeostasis...
  48. ncbi The orally bioavailable met inhibitor PF-2341066 inhibits osteosarcoma growth and osteolysis/matrix production in a xenograft model
    Erik R Sampson
    Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY 14642, USA
    J Bone Miner Res 26:1283-94. 2011
    ..PF-2341066 may represent an effective new systemic therapy for localized and potentially disseminated osteosarcoma...
  49. ncbi Titanium particles stimulate COX-2 expression in synovial fibroblasts through an oxidative stress-induced, calpain-dependent, NF-kappaB pathway
    Xiaochao Wei
    Center for Musculoskeletal Research, Univ of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA
    Am J Physiol Cell Physiol 297:C310-20. 2009
    ..These findings define important targets for osteolysis but may also have importance in other diseases where fibroblasts respond to environmental particles, including pulmonary diseases...
  50. ncbi Growth plate chondrocyte maturation is regulated by basal intracellular calcium
    Michael J Zuscik
    Center for Musculoskeletal Research, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA
    Exp Cell Res 276:310-9. 2002
    ..These findings underscore the importance of cellular Ca(2+) in GPC function and suggest that PTHrP action in the growth plate is at least partially regulated by changes in basal [Ca(2+)](i)...
  51. ncbi Smad3-deficient chondrocytes have enhanced BMP signaling and accelerated differentiation
    Tian Fang Li
    Center for Musculoskeletal Research, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA
    J Bone Miner Res 21:4-16. 2006
    ..Smad2 or Smad3 overexpression and BMP blockade abrogate accelerated maturation in Smad3-/- chondrocytes. BMP signaling is increased in TGF-beta deficiency and is required for accelerated chondrocyte maturation...
  52. ncbi Overlapping expression of Runx1(Cbfa2) and Runx2(Cbfa1) transcription factors supports cooperative induction of skeletal development
    Nathan Smith
    The Center for Musculoskeletal Research, University of Rochester, Rochester, New York, USA
    J Cell Physiol 203:133-43. 2005
    ....
  53. ncbi Freeze-dried tendon allografts as tissue-engineering scaffolds for Gdf5 gene delivery
    Patrick Basile
    Center for Musculoskeletal Research, Department of Orthopaedics, University of Rochester, Rochester, New York 14642, USA
    Mol Ther 16:466-73. 2008
    ..Collectively, our data demonstrate the feasibility and efficacy of therapeutic tendon allograft processing as a novel paradigm in tissue engineering in order to address difficult clinical problems such as tendon adhesions...
  54. ncbi Evaluation of dense polylactic acid/beta-tricalcium phosphate scaffolds for bone tissue engineering
    Laura Yanoso-Scholl
    Department of Biomedical Engineering, University of Rochester, Rochester, New York, USA
    J Biomed Mater Res A 95:717-26. 2010
    ..8-fold increase in neo vessel formation. In conclusion, dense PLA/beta-TCP scaffolds can be engineered with enhanced mechanical properties and potentially be exploited for localized therapeutic factor delivery...
  55. ncbi Transforming growth factor-beta and Wnt signals regulate chondrocyte differentiation through Twist1 in a stage-specific manner
    Yu Feng Dong
    Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, New York 14642, USA
    Mol Endocrinol 21:2805-20. 2007
    ..Together, our findings show that Twist1 may be an important regulator of chondrocyte progression toward terminal maturation in response to TGF-beta and canonical Wnt signaling...
  56. ncbi Cyclooxygenase-2 regulates mesenchymal cell differentiation into the osteoblast lineage and is critically involved in bone repair
    Xinping Zhang
    The Center for Musculoskeletal Research, University of Rochester Medical Center, New York 14642, USA
    J Clin Invest 109:1405-15. 2002
    ..These results provide a model whereby COX-2 regulates the induction of cbfa1 and osterix to mediate normal skeletal repair...
  57. ncbi Self-complementary AAV2.5-BMP2-coated femoral allografts mediated superior bone healing versus live autografts in mice with equivalent biomechanics to unfractured femur
    Cemal Yazici
    The Center for Musculoskeletal Research, University of Rochester, Rochester, New York, USA
    Mol Ther 19:1416-25. 2011
    ..Collectively, these results demonstrate that scAAV2.5-BMP2 coating overcomes the major limitations of structural allografts, which can be used to heal critical defects of any size...
  58. ncbi Generation of a transgenic mouse model with chondrocyte-specific and tamoxifen-inducible expression of Cre recombinase
    Mo Chen
    Department of Orthopaedics, Center for Musculoskeletal Research, University of Rochester School of Medicine, Rochester, New York 14642, USA
    Genesis 45:44-50. 2007
    ..These results demonstrate that Col2a1-CreER(T2) transgenic mice can be used as a valuable tool for an inducible and chondrocyte-specific gene deletion approach...
  59. ncbi BMP2, but not BMP4, is crucial for chondrocyte proliferation and maturation during endochondral bone development
    Bing Shu
    Department of Orthopaedics and Rehabilitation, Center for Musculoskeletal Research, University of Rochester School of Medicine, Rochester, NY 14642, USA
    J Cell Sci 124:3428-40. 2011
    ..Our studies provide novel insights into the genetic control and molecular mechanism of BMP signaling during cartilage development...
  60. ncbi Systemic tumor necrosis factor alpha mediates an increase in peripheral CD11bhigh osteoclast precursors in tumor necrosis factor alpha-transgenic mice
    Ping Li
    University of Rochester Medical Center, Rochester, New York 14642, USA
    Arthritis Rheum 50:265-76. 2004
    ..To investigate the mechanisms whereby tumor necrosis factor alpha (TNFalpha) increases osteoclastogenesis in vivo...
  61. ncbi Teriparatide therapy enhances devitalized femoral allograft osseointegration and biomechanics in a murine model
    David G Reynolds
    Department of Biomedical Engineering, University of Rochester, Rochester, NY, USA
    Bone 48:562-70. 2011
    ....
  62. ncbi Primary murine limb bud mesenchymal cells in long-term culture complete chondrocyte differentiation: TGF-beta delays hypertrophy and PGE2 inhibits terminal differentiation
    Xinping Zhang
    Department of Orthopaedics, Center for Musculoskeletal Research, University of Rochester, Rochester, NY 14642, USA
    Bone 34:809-17. 2004
    ....
  63. ncbi Axin2 controls bone remodeling through the beta-catenin-BMP signaling pathway in adult mice
    Ying Yan
    Department of Orthopaedics, Center for Musculoskeletal Research, University of Rochester School of Medicine, Rochester, NY 14642, USA
    J Cell Sci 122:3566-78. 2009
    ..Taken together, our findings demonstrate that Axin2 is a key negative regulator in bone remodeling in adult mice and regulates osteoblast differentiation through the beta-catenin-BMP2/4-Osx signaling pathway in osteoblasts...
  64. ncbi Recombinant adeno-associated virus-mediated osteoprotegerin gene therapy inhibits wear debris-induced osteolysis
    Michael Ulrich-Vinther
    Department of Orthopedics, Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY 14642, USA
    J Bone Joint Surg Am 84:1405-12. 2002
    ..This study investigated whether gene therapy using a recombinant adeno-associated viral vector that expresses OPG can inhibit wear debris-induced osteolysis...
  65. ncbi Differential effects of biologic versus bisphosphonate inhibition of wear debris-induced osteolysis assessed by longitudinal micro-CT
    Ryosuke Tsutsumi
    The Center for Musculoskeletal Research, University of Rochester, 601 Elmwood Avenue, Box 665, Rochester, New York 14642 0001, USA
    J Orthop Res 26:1340-6. 2008
    ..001)...
  66. ncbi Tamoxifen-inducible CreER-mediated gene targeting in periosteum via bone-graft transplantation
    Chao Xie
    The Center for Musculoskeletal Research, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA
    J Bone Joint Surg Am 90:9-13. 2008
    ..Our current approach overcomes this encumbrance and enables examination of gene function in a time-dependent and repair-tissue-specific manner...
  67. ncbi Quantitative mouse model of implant-associated osteomyelitis and the kinetics of microbial growth, osteolysis, and humoral immunity
    Dan Li
    The Center for Musculoskeletal Research, University of Rochester Medical Center, 601 Elmwood Avenue, Box 665, Rochester, New York 14642, USA
    J Orthop Res 26:96-105. 2008
    ..05). Collectively, these studies demonstrate the first quantitative model of implant-associated OM that defines the kinetics of microbial growth, osteolysis, and humoral immunity following infection...
  68. ncbi Clinical relevance of increased retinoid and cAMP transcriptional programs in tumor cells rendered non-malignant by dominant negative inhibition of NFkappaB
    Valentine B Andela
    Center for Musculoskeletal Research, University of Rochester Medical Center, 575 Elmwood Avenue, 1 7534, Rochester, NY 14642, USA
    Cancer Lett 194:37-43. 2003
    ..Our results are consistent with the putative role of retinoids and cAMP in the malignant reversion of tumor cells and illustrative of the binary nature of transcriptional programs that modulate malignant progression...
  69. ncbi Smad6 interacts with Runx2 and mediates Smad ubiquitin regulatory factor 1-induced Runx2 degradation
    Run Shen
    Department of Orthopaedics and Department of Pathology, Center for Musculoskeletal Research, University of Rochester, School of Medicine, Rochester, New York 14642, USA
    J Biol Chem 281:3569-76. 2006
    ..Smurf1-induced Runx2 degradation serves as a negative regulatory mechanism for the BMP-Smad-Runx2 signaling pathway...
  70. ncbi Structural bone allograft combined with genetically engineered mesenchymal stem cells as a novel platform for bone tissue engineering
    Chao Xie
    Center for Musculoskeletal Research, University of Rochester, School of Medicine and Dentistry, Rochester, New York 14642, USA
    Tissue Eng 13:435-45. 2007
    ..Taken together, we propose a novel strategy to combine structural bone allograft with genetically engineered mesenchymal stem cells as a novel platform for bone tissue engineering...
  71. ncbi Remodeling of cortical bone allografts mediated by adherent rAAV-RANKL and VEGF gene therapy
    Hiromu Ito
    The Center for Musculoskeletal Research, University of Rochester, 601 Elmwood Avenue, Box 665, Rochester, New York 14642, USA
    Nat Med 11:291-7. 2005
    ..In conclusion, we find that RANKL and VEGF are necessary and sufficient for efficient autograft remodeling and can be transferred using rAAV to revitalize structural allografts...
  72. ncbi Maximizing immune responses: the effects of covalent peptide linkage to beta-2-microglobulin
    Stephen M Bauer
    Division of Pulmonary and Critical Care Medicine, University of Rochester School of Medicine, Rochester, NY 14642 8692, USA
    Oncol Res 17:205-16. 2008
    ..We conclude that vaccines incorporating peptides covalently linked to beta2m may have future potential in the specific targeting of human malignancy...
  73. ncbi A perspective: engineering periosteum for structural bone graft healing
    Xinping Zhang
    The Center for Musculoskeletal Research, University of Rochester Medical Center, School of Medicine and Dentistry, 601 Elmwood Avenue, Rochester, NY 14642, USA
    Clin Orthop Relat Res 466:1777-87. 2008
    ....
  74. ncbi PGE2 inhibits chondrocyte differentiation through PKA and PKC signaling
    Tian-Fang Li
    Center for Musculoskeletal Research, School of Medicine and Dentistry, University of Rochester, Rochester, NY 14642, USA
    Exp Cell Res 300:159-69. 2004
    ..These observations demonstrate potent prostaglandin regulatory effects on chondrocyte maturation and show a role for both PKA and PKC signaling in PGE2 regulatory events...
  75. ncbi Recent advances in gene delivery for structural bone allografts
    Hani A Awad
    Department of Biomedical Engineering, The Center for Musculoskeletal Research, University of Rochester, Rochester, New York 14620, USA
    Tissue Eng 13:1973-85. 2007
    ..Therefore, innovations in gene delivery offer promising therapeutic approaches for tissue engineering of structural bone substitutes that can potentially have clinical applications in challenging indications...
  76. ncbi Biological effects of rAAV-caAlk2 coating on structural allograft healing
    Mette Koefoed
    The Center for Musculoskeletal Research, University of Rochester, 601 Elmwood Avenue, Rochester, NY 14642, USA
    Mol Ther 12:212-8. 2005
    ..These results indicate that cell-free, rAAV-coated allografts have the potential to revitalize in vivo following transplantation...
  77. ncbi Regulation of chondrogenesis and chondrocyte differentiation by stress
    Michael J Zuscik
    Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, New York 14642, USA
    J Clin Invest 118:429-38. 2008
    ..A summary of the influence of the most well-understood normal and pathologic stressors on the differentiation program is also presented...
  78. ncbi A novel murine segmental femoral graft model
    Prarop Tiyapatanaputi
    Department of Orthopaedics, The Center for Musculoskeletal Research, University of Rochester Medical Center, 601 Elmwood Avenue, NY 14642, USA
    J Orthop Res 22:1254-60. 2004
    ..This small animal model of structural bone grafting can be used to evaluate tissue-engineered allografts and novel bone graft substitutes using quantitative and molecularly defined outcome measures...
  79. ncbi Micro-computed tomography prediction of biomechanical strength in murine structural bone grafts
    David G Reynolds
    Department of Biomedical Engineering, University of Rochester, Rochester, NY 14620, USA
    J Biomech 40:3178-86. 2007
    ..The statistical correlations approach used in this mouse study could be useful in guiding future development of non-invasive predictors of the biomechanical properties of allografts using clinical CT...
  80. ncbi Differential regulation of EP receptor isoforms during chondrogenesis and chondrocyte maturation
    Christine A Clark
    Center for Musculoskeletal Research, University of Rochester, School of Medicine and Dentistry, Rochester, NY 14642, USA
    Biochem Biophys Res Commun 328:764-76. 2005
    ....
  81. ncbi The effect of surface demineralization of cortical bone allograft on the properties of recombinant adeno-associated virus coatings
    Cemal Yazici
    The Center for Musculoskeletal Research, University of Rochester, 601 Elmwood Avenue, Rochester, NY 14642, USA
    Biomaterials 29:3882-7. 2008
    ..Thus, surface demineralization of human cortical bone allograft increases its absorbance for uniform rAAV coating, without affecting vector transduction efficiency...
  82. ncbi Lead exposure inhibits fracture healing and is associated with increased chondrogenesis, delay in cartilage mineralization, and a decrease in osteoprogenitor frequency
    Jonathan J Carmouche
    Center for Musculoskeletal Research, University of Rochester Medical Center, University of Rochester, School of Medicine and Dentistry, Rochester, New York 14642, USA
    Environ Health Perspect 113:749-55. 2005
    ..We conclude that Pb delays fracture healing at environmentally relevant doses and induces fibrous nonunions at higher doses by inhibiting the progression of endochondral ossification...
  83. ncbi PGE2 and IL-6 production by fibroblasts in response to titanium wear debris particles is mediated through a Cox-2 dependent pathway
    Susan V Bukata
    The Department of Orthopaedics, University of Rochester Medical Center, Center for Musculoskeletal Research, 601 Elmwood Avenue, Box 665, Rochester, NY 14642, USA
    J Orthop Res 22:6-12. 2004
    ....
  84. ncbi COX-1 and COX-2 expression in osteoid osteomas
    David V Mungo
    Department of Orthopaedics, Medical Center, University of Rochester, NY 14642, USA
    J Orthop Res 20:159-62. 2002
    ..These findings suggest that the newly selective COX-2 inhibitors could be used to more safely treat osteoid osteomas...

Research Grants31

  1. Cyclooxygenases in Skeletal Repair
    REGIS O KEEFE; Fiscal Year: 2007
    ..In all, the proposal contains state of the art molecular methods to comprehensively investigate a critically important issue with a high degree of clinical relevance. ..
  2. Training in Orthopaedic Research
    REGIS O KEEFE; Fiscal Year: 2007
    ....
  3. Prostaglandin Signaling in Wear Debris-induced Osteolysis
    REGIS O KEEFE; Fiscal Year: 2007
    ....
  4. The use of genetic models to define the role of beta-catenin in post-natal growth
    REGIS O KEEFE; Fiscal Year: 2007
    ..The proposed studies will provide critical new insights regarding cartilage diseases including chondrodysplasia, bone repair, and osteoarthritis. ..
  5. Prostaglandin Signaling in Wear Debris-induced Osteolysis
    REGIS O KEEFE; Fiscal Year: 2009
    ....
  6. The use of genetic models to define the role of beta-catenin in post-natal growth
    REGIS O KEEFE; Fiscal Year: 2009
    ..The proposed studies will provide critical new insights regarding cartilage diseases including chondrodysplasia, bone repair, and osteoarthritis. ..
  7. Cyclooxygenases in Skeletal Repair
    REGIS O KEEFE; Fiscal Year: 2009
    ..Insights gained from this work will enhance the understanding and treatment of fractures in patients with compromised healing, and has particular potential to improve bone repair in the elderly. ..
  8. Cyclooxygenases in Skeletal Repair
    Xinping Zhang; Fiscal Year: 2010
    ..Insights gained from this work will enhance the understanding and treatment of fractures in patients with compromised healing, and has particular potential to improve bone repair in the elderly. ..
  9. GROWTH FACTORS AND EPIPHYSEAL CHONDROCYTE MATURATION
    REGIS O KEEFE; Fiscal Year: 2006
    ....
  10. GROWTH FACTORS AND EPIPHYSEAL CHONDROCYTE MATURATION
    REGIS O KEEFE; Fiscal Year: 2001
    ..Finally, the hypothesis that epiphyseal chondrocytes inhibit the maturation of growth plate will be tested using chondrocytes in co-culture experiments. ..
  11. GENE THERAPY FOR PROSTHETIC LOOSENING
    REGIS O KEEFE; Fiscal Year: 2003
    ....
  12. The use of genetic models to define the role of beta-catenin in post-natal growth
    REGIS J O apos KEEFE; Fiscal Year: 2010
    ..The proposed studies will provide critical new insights regarding cartilage diseases including chondrodysplasia, bone repair, and osteoarthritis. ..