Karl Jepsen

Summary

Affiliation: Mount Sinai School of Medicine
Country: USA

Publications

  1. pmc Functional interactions among morphologic and tissue quality traits define bone quality
    Karl J Jepsen
    Leni and Peter W May Department of Orthopaedics, Mount Sinai School of Medicine, Box 1188, One Gustave Levy Place, New York, NY 10029, USA
    Clin Orthop Relat Res 469:2150-9. 2011
  2. pmc Phenotypic integration of skeletal traits during growth buffers genetic variants affecting the slenderness of femora in inbred mouse strains
    Karl J Jepsen
    Leni and Peter W May Department of Orthopaedics, Mount Sinai School of Medicine, New York, NY 10029, USA
    Mamm Genome 20:21-33. 2009
  3. pmc Genetic randomization reveals functional relationships among morphologic and tissue-quality traits that contribute to bone strength and fragility
    Karl J Jepsen
    Leni and Peter W May Department of Orthopaedics, Mount Sinai School of Medicine, New York, New York, USA
    Mamm Genome 18:492-507. 2007
  4. pmc Systems analysis of bone
    Karl J Jepsen
    Leni and Peter W May Department of Orthopaedics, Mount Sinai School of Medicine, New York, NY 10029, USA
    Wiley Interdiscip Rev Syst Biol Med 1:73-88. 2009
  5. ncbi request reprint Hierarchical relationship between bone traits and mechanical properties in inbred mice
    Karl J Jepsen
    Department of Orthopaedics, Box 1188, Mount Sinai School of Medicine, One Gustave Levy Place, New York, New York 10029, USA
    Mamm Genome 14:97-104. 2003
  6. pmc Genetically determined phenotype covariation networks control bone strength
    Karl J Jepsen
    Leni and Peter W May Department of Orthopaedics, Mount Sinai School of Medicine, New York, NY 10029, USA
    J Bone Miner Res 25:1581-93. 2010
  7. ncbi request reprint Genetic background influences cortical bone response to ovariectomy
    Chao Yang Li
    Leni and Peter W May Department of Orthopaedics, Mount Sinai School of Medicine, New York, New York, USA
    J Bone Miner Res 20:2150-8. 2005
  8. ncbi request reprint Genetic variation in structure-function relationships for the inbred mouse lumbar vertebral body
    Steven M Tommasini
    New York Center for Biomedical Engineering, CUNY Graduate School, Department of Biomedical Engineering, City College of New York, New York, New York, USA
    J Bone Miner Res 20:817-27. 2005
  9. pmc Genetic variation in mouse femoral tissue-level mineral content underlies differences in whole bone mechanical properties
    Hayden William Courtland
    Leni and Peter W May Department of Orthopaedics, Mount Sinai School of Medicine, New York, NY 10029, USA
    Cells Tissues Organs 189:237-40. 2009
  10. ncbi request reprint Genetic variation in bone growth patterns defines adult mouse bone fragility
    Christopher Price
    Leni and Peter W May Department of Orthopaedics, Mount Sinai School of Medicine, New York, New York 10029, USA
    J Bone Miner Res 20:1983-91. 2005

Research Grants

Detail Information

Publications39

  1. pmc Functional interactions among morphologic and tissue quality traits define bone quality
    Karl J Jepsen
    Leni and Peter W May Department of Orthopaedics, Mount Sinai School of Medicine, Box 1188, One Gustave Levy Place, New York, NY 10029, USA
    Clin Orthop Relat Res 469:2150-9. 2011
    ..Advances in diagnostic and treatment regimens that aim to reduce fracture incidence will benefit from a better understanding of how bone morphology and tissue quality define whole-bone mechanical properties...
  2. pmc Phenotypic integration of skeletal traits during growth buffers genetic variants affecting the slenderness of femora in inbred mouse strains
    Karl J Jepsen
    Leni and Peter W May Department of Orthopaedics, Mount Sinai School of Medicine, New York, NY 10029, USA
    Mamm Genome 20:21-33. 2009
    ..Variants that impair this process or that cannot be fully compensated are expected to alter skeletal growth leading to underdesigned (weak) or overdesigned (bulky) structures...
  3. pmc Genetic randomization reveals functional relationships among morphologic and tissue-quality traits that contribute to bone strength and fragility
    Karl J Jepsen
    Leni and Peter W May Department of Orthopaedics, Mount Sinai School of Medicine, New York, New York, USA
    Mamm Genome 18:492-507. 2007
    ..Genetic or environmental perturbations that alter these functional interactions during growth would be expected to lead to loss of function and suboptimal adult bone quality...
  4. pmc Systems analysis of bone
    Karl J Jepsen
    Leni and Peter W May Department of Orthopaedics, Mount Sinai School of Medicine, New York, NY 10029, USA
    Wiley Interdiscip Rev Syst Biol Med 1:73-88. 2009
    ..This information will provide novel approaches to assessing skeletal health during growth and aging and for developing novel treatment strategies to reduce the morbidity and mortality associated with fragility fractures...
  5. ncbi request reprint Hierarchical relationship between bone traits and mechanical properties in inbred mice
    Karl J Jepsen
    Department of Orthopaedics, Box 1188, Mount Sinai School of Medicine, One Gustave Levy Place, New York, New York 10029, USA
    Mamm Genome 14:97-104. 2003
    ..Moreover, because the traits we examined are measurable with non-invasive means, this approach may also prove directly applicable to osteoporosis risk assessment...
  6. pmc Genetically determined phenotype covariation networks control bone strength
    Karl J Jepsen
    Leni and Peter W May Department of Orthopaedics, Mount Sinai School of Medicine, New York, NY 10029, USA
    J Bone Miner Res 25:1581-93. 2010
    ....
  7. ncbi request reprint Genetic background influences cortical bone response to ovariectomy
    Chao Yang Li
    Leni and Peter W May Department of Orthopaedics, Mount Sinai School of Medicine, New York, New York, USA
    J Bone Miner Res 20:2150-8. 2005
    ..Inbred mice were ovariectomized at 16 weeks of age and killed at three time-points after surgery. We found that the variation in estrogen deficit-related cortical bone loss is genetically determined...
  8. ncbi request reprint Genetic variation in structure-function relationships for the inbred mouse lumbar vertebral body
    Steven M Tommasini
    New York Center for Biomedical Engineering, CUNY Graduate School, Department of Biomedical Engineering, City College of New York, New York, New York, USA
    J Bone Miner Res 20:817-27. 2005
    ..Genetic variability in whole bone mechanical properties could be explained by a combination of the traits specifying the amount, distribution, and quality of the cortical and trabecular bone tissue...
  9. pmc Genetic variation in mouse femoral tissue-level mineral content underlies differences in whole bone mechanical properties
    Hayden William Courtland
    Leni and Peter W May Department of Orthopaedics, Mount Sinai School of Medicine, New York, NY 10029, USA
    Cells Tissues Organs 189:237-40. 2009
    ..The greater stiffness and brittleness of A/J femora are likely due to differential biological control (osteoblast activity) of the amount of mineral...
  10. ncbi request reprint Genetic variation in bone growth patterns defines adult mouse bone fragility
    Christopher Price
    Leni and Peter W May Department of Orthopaedics, Mount Sinai School of Medicine, New York, New York 10029, USA
    J Bone Miner Res 20:1983-91. 2005
    ..5 and 1 year. Genotype-specific variation in postnatal, pubertal, and postpubertal growth patterns and mineral accrual explained differences in adult bone trait combinations and thus bone fragility...
  11. pmc Genetic variation in the patterns of skeletal progenitor cell differentiation and progression during endochondral bone formation affects the rate of fracture healing
    Karl J Jepsen
    Department of Orthopaedics, Mount Sinai School of Medicine, New York, New York, USA
    J Bone Miner Res 23:1204-16. 2008
    ..These results show that (1) different strains of mice express variations of skeletal stem cell lineage differentiation and (2) that these variations affect the rate of fracture healing...
  12. pmc Elevated serum levels of IGF-1 are sufficient to establish normal body size and skeletal properties even in the absence of tissue IGF-1
    Sebastien Elis
    Division of Endocrinology, Diabetes and Bone Disease, Mount Sinai School of Medicine, New York, NY 10029 6574, USA
    J Bone Miner Res 25:1257-66. 2010
    ..Our data indicate that in the absence of tissue igf1 gene expression, maintaining long-term elevations in serum IGF-1 is sufficient to establish normal body size, body composition, and both skeletal architecture and mechanical function...
  13. pmc Involvement of the Toll-like receptor 4 pathway and use of TNF-alpha antagonists for treatment of the mucopolysaccharidoses
    Calogera M Simonaro
    Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, NY 10029, USA
    Proc Natl Acad Sci U S A 107:222-7. 2010
    ..These studies revealed the important role of TLR4 signaling in MPS bone and joint disease and suggest that targeting TNF-alpha may have positive therapeutic effects...
  14. pmc Fourier transform infrared imaging microspectroscopy and tissue-level mechanical testing reveal intraspecies variation in mouse bone mineral and matrix composition
    Hayden William Courtland
    Division of Endocrinology, Diabetes, and Bone Diseases, Mount Sinai School of Medicine, New York, NY, USA
    Calcif Tissue Int 83:342-53. 2008
    ..These results suggest that specific combinations of bone quality and morphological traits are genetically regulated such that mechanically functional bones can be constructed in different ways...
  15. pmc Type 2 diabetic mice demonstrate slender long bones with increased fragility secondary to increased osteoclastogenesis
    Yuki Kawashima
    Division of Endocrinology, Diabetes and Bone Diseases, Mount Sinai School of Medicine, New York, NY 10029, USA
    Bone 44:648-55. 2009
    ..Further, these results emphasize the importance of evaluating diabetic bone based on morphology in addition to bone mass...
  16. pmc Serum IGF-1 determines skeletal strength by regulating subperiosteal expansion and trait interactions
    Shoshana Yakar
    Division of Endocrinology, Diabetes and Bone Disease, Mount Sinai School of Medicine, New York, New York 10029 6574, USA
    J Bone Miner Res 24:1481-92. 2009
    ....
  17. ncbi request reprint A biomechanical comparison of two patterns of screw insertion
    Sheldon Lichtblau
    Peter and Leni May Department of Orthopaedic Surgery, Mount Sinai School of Medicine, Mount Sinai Medical Center, New York, New York, USA
    Bull NYU Hosp Jt Dis 66:269-71. 2008
    ..The vertical pattern of screw insertion is less apt to predispose a long bone to subsequent fracture than a horizontal pattern...
  18. ncbi request reprint Mice lacking cathepsin K maintain bone remodeling but develop bone fragility despite high bone mass
    Chao Yang Li
    Leni and Peter W May Department of Orthopaedics, Mount Sinai School of Medicine, New York 10029 6574, USA
    J Bone Miner Res 21:865-75. 2006
    ....
  19. pmc Biological co-adaptation of morphological and composition traits contributes to mechanical functionality and skeletal fragility
    Steven M Tommasini
    New York Center for Biomedical Engineering, CUNY Graduate School, Department of Biomedical Engineering, City College of New York, New York, New York, USA
    J Bone Miner Res 23:236-46. 2008
    ..However, certain sets of traits are expected to perform poorly under extreme load conditions...
  20. pmc Phenotypic integration among trabecular and cortical bone traits establishes mechanical functionality of inbred mouse vertebrae
    Steven M Tommasini
    New York Center for Biomedical Engineering, CUNY Graduate Center, Department of Biomedical Engineering, City College of New York, New York, New York, USA
    J Bone Miner Res 24:606-20. 2009
    ..The covariation among corticocancellous traits has important implications for genetic analyses and for interpreting the response of bone to genetic and environmental perturbations...
  21. pmc Early response to tendon fatigue damage accumulation in a novel in vivo model
    David T Fung
    Leni and Peter W May Department of Orthopaedics, Mount Sinai School of Medicine, 5 East 98th Street, 9th Floor, NY 10029, USA
    J Biomech 43:274-9. 2010
    ..Further, structural repair may not be initiated until reaching end-stage fatigue life, where the repair response may unable to restore the damaged tendon to its pre-fatigue architecture...
  22. ncbi request reprint A syndrome of joint laxity and impaired tendon integrity in lumican- and fibromodulin-deficient mice
    Karl J Jepsen
    Department of Orthopedics, Mount Sinai School of Medicine, New York, New York 10029, USA
    J Biol Chem 277:35532-40. 2002
    ..This study demonstrates that the collagen fibril-modifying proteoglycans, lumican and fibromodulin, are candidate genes and key players in the pathogenesis of certain types of Ehlers-Danlos syndrome and other connective tissue disorders...
  23. pmc Serum complexes of insulin-like growth factor-1 modulate skeletal integrity and carbohydrate metabolism
    Shoshana Yakar
    Endocrinology Diabetes and Bone Disease, The Mt Sinai School of Medicine, One Gustave L Levy Place, Box 1055, New York, NY 10029 6574, USA
    FASEB J 23:709-19. 2009
    ..3) IGFBP-3 deficiency resulted in increased linear growth. In summary, each IGF-1 complex constituent appears to play a distinct role in determining skeletal phenotype, with different effects on cortical and trabecular bone compartments...
  24. ncbi request reprint Sexual dimorphism affects tibia size and shape but not tissue-level mechanical properties
    Steven M Tommasini
    New York Center for Biomedical Engineering, CUNY Graduate School, Department of Biomedical Engineering, City College of New York, New York, NY, USA
    Bone 40:498-505. 2007
    ..This may be a contributing factor to the greater incidence of stress fractures observed for female military recruits...
  25. pmc Percolation theory relates corticocancellous architecture to mechanical function in vertebrae of inbred mouse strains
    Steven M Tommasini
    Department of Biomedical Engineering, City College of New York CUNY, Convent Avenue at 138th Street, New York, NY 10021, USA
    Bone 42:743-50. 2008
    ....
  26. pmc Interindividual variation in functionally adapted trait sets is established during postnatal growth and predictable based on bone robustness
    Nirnimesh Pandey
    Leni and Peter W May Department of Orthopaedics, Mount Sinai School of Medicine, New York, New York 10029, USA
    J Bone Miner Res 24:1969-80. 2009
    ..Considering the natural variation in acquired trait sets may help identify determinants of fracture risk, because age-related bone loss and gain will affect slender and robust structures differently...
  27. ncbi request reprint Relationship between bone morphology and bone quality in male tibias: implications for stress fracture risk
    Steven M Tommasini
    New York Center for Biomedical Engineering, CUNY Graduate School, Department of Biomedical Engineering, City College of New York, New York, USA
    J Bone Miner Res 20:1372-80. 2005
    ..Tissue-level mechanical properties varied with bone size. Narrower tibias were comprised of tissue that was more brittle and more prone to accumulating damage compared with tissue from wider tibias...
  28. ncbi request reprint Hydrostatic pressure induces apoptosis in human chondrocytes from osteoarthritic cartilage through up-regulation of tumor necrosis factor-alpha, inducible nitric oxide synthase, p53, c-myc, and bax-alpha, and suppression of bcl-2
    Najmul Islam
    Department of Orthopaedics, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106 4946, USA
    J Cell Biochem 87:266-78. 2002
    ..These results indicated that HP is a strong inducer of apoptosis in osteoarthritic human chondrocytes in vitro...
  29. doi request reprint Cycle-dependent matrix remodeling gene expression response in fatigue-loaded rat patellar tendons
    Hui B Sun
    Leni and Peter W May Department of Orthopaedics, Mount Sinai School of Medicine, One Gustave L Levy Place, Box 1188, New York, New York 10029, USA
    J Orthop Res 28:1380-6. 2010
    ..Differences found in tendon response to high- and low-cycle loading are suggestive of the underlying mechanisms associated with a healthy or damaging response...
  30. doi request reprint Subrupture tendon fatigue damage
    David T Fung
    Leni and Peter W May Department of Orthopaedics, Mount Sinai School of Medicine, New York, New York 10029, USA
    J Orthop Res 27:264-73. 2009
    ..The current findings characterized the sequential, microstructural events that underlie the tendon fatigue process and indicate that tendon deformation can be used to accurately assess the progression of damage accumulation in tendons...
  31. ncbi request reprint Variability in tendon and knee joint biomechanics among inbred mouse strains
    Vincent M Wang
    Department of Orthopaedic Surgery, Rush University Medical Center, 765A Armour Academic Facility, 600 South Paulina Street, Chicago, IL 60612, USA
    J Orthop Res 24:1200-7. 2006
    ..Therefore, the three inbred strains constitute a useful experimental model to elucidate genetic control of structure-function relationships in normal and healing tendons and ligaments...
  32. ncbi request reprint Targeted overexpression of androgen receptor in osteoblasts: unexpected complex bone phenotype in growing animals
    Kristine M Wiren
    Base and Mineral Research Unit, Portland Veterans Affairs Medical Center P3 R and D39, 3710 Southwest Veterans Hospital Road, Portland, Oregon 97239, USA
    Endocrinology 145:3507-22. 2004
    ..These results indicate that AR action is important in the development of a sexually dimorphic skeleton and argue for a direct role for androgen transactivation of AR in osteoblasts in modulating skeletal development and homeostasis...
  33. ncbi request reprint Relationship between damage accumulation and mechanical property degradation in cortical bone: microcrack orientation is important
    Ozan Akkus
    Department of Bioengineering, MS 303, Orthopaedic Bioengineering Laboratory, The University of Toledo, Toledo, Ohio 43606 3390, USA
    J Biomed Mater Res A 65:482-8. 2003
    ..180). We conclude that microcrack orientation is an essential physical variable in the relationship between damage accumulation and degradation of mechanical properties of cortical bone tissue...
  34. ncbi request reprint The aging cortex: to crack or not to crack
    Karl J Jepsen
    Osteoporos Int 14:S57-62; discussion S63-66. 2003
  35. ncbi request reprint The Collaborative Cross, a community resource for the genetic analysis of complex traits
    Gary A Churchill
    The Jackson Laboratory, 600 Main Street Bar Harbor, Maine 04609, USA
    Nat Genet 36:1133-7. 2004
    ..The Collaborative Cross will provide a common reference panel specifically designed for the integrative analysis of complex systems and will change the way we approach human health and disease...
  36. ncbi request reprint Long-term disuse osteoporosis seems less sensitive to bisphosphonate treatment than other osteoporosis
    Chao Yang Li
    Leni and Peter W May Department of Orthopaedics, Mount Sinai School of Medicine, New York, New York 10029 6574, USA
    J Bone Miner Res 20:117-24. 2005
    ..Risedronate slowed cortical thinning and partially preserved mechanical properties, but it was unable to suppress bone loss to the degree seen in other osteoporoses...
  37. ncbi request reprint Three-dimensional reconstruction of fracture callus morphogenesis
    Louis C Gerstenfeld
    Orthopaedic Research Laboratory, Boston University Medical Center, 715 Albany Street, R 205, Boston, MA 02118, USA
    J Histochem Cytochem 54:1215-28. 2006
    ..These data further show that remodeling of the calcified cartilage produces a trabecular bone structure unique to fracture healing that provides the rapid regain in weight-bearing capacity to the injured bone...
  38. pmc The effect of recovery time and test conditions on viscoelastic measures of tensile damage in cortical bone
    Won Joo
    Musculoskeletal Mechanics and Materials Laboratory, Department of Mechanical and Aerospace Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA
    J Biomech 40:2731-7. 2007
    ..The results demonstrate that choice of test conditions can influence the apparent magnitude of damage effects. They also indicate that 10 min recovery time was sufficient to stabilize most measures of the damage state...
  39. pmc Targeting of androgen receptor in bone reveals a lack of androgen anabolic action and inhibition of osteogenesis: a model for compartment-specific androgen action in the skeleton
    Kristine M Wiren
    Bone and Mineral Research Unit, Portland Veterans Affairs Medical Center, Portland, Oregon, USA
    Bone 43:440-51. 2008
    ..These results indicate that direct androgen action in mature osteoblasts is not anabolic, and raise concerns regarding anabolic steroid abuse in the developing skeleton or high-dose treatment in eugonadal adults...

Research Grants9

  1. GENETIC DETERMINATION OF SKELETAL FRAGILITY
    Karl Jepsen; Fiscal Year: 2002
    ..and (3) identifying a genetic basis for skeletal fragility may lead to a better understanding of how to customize treatment modalities to accommodate those individuals who are resistant to traditional treatment strategies. ..
  2. GENETIC DETERMINATION OF SKELETAL FRAGILITY
    Karl Jepsen; Fiscal Year: 2007
    ..These functional interactions are critically important for developing a comprehensive systems analysis of bone that will generate genetic-based strategies for early diagnosis and prophylactic treatment of osteoporosis. ..
  3. GENETIC DETERMINATION OF SKELETAL FRAGILITY
    Karl J Jepsen; Fiscal Year: 2010
    ....
  4. Functionality and Fracture Susceptibility of Corticocancellous Structures
    Karl J Jepsen; Fiscal Year: 2010
    ..This systems analysis, which examines the relationship among traits in the context of functionality, will provide new insight into the genetic basis of fracture susceptibility. ..