Research Topics
Species | Karl JepsenSummaryAffiliation: Mount Sinai School of Medicine Country: USA Publications
Research Grants
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Detail Information
Publications
Functional interactions among morphologic and tissue quality traits define bone qualityKarl 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...- Phenotypic integration of skeletal traits during growth buffers genetic variants affecting the slenderness of femora in inbred mouse strainsKarl 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... - Genetic randomization reveals functional relationships among morphologic and tissue-quality traits that contribute to bone strength and fragilityKarl 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... - Systems analysis of boneKarl 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... 
Hierarchical relationship between bone traits and mechanical properties in inbred miceKarl 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...- Genetically determined phenotype covariation networks control bone strengthKarl 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.... - Genetic background influences cortical bone response to ovariectomyChao 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..Our results suggest that patterns of estrogen deficit-associated cortical bone loss are genetically determined... - Genetic variation in structure-function relationships for the inbred mouse lumbar vertebral bodySteven 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..Therefore, considering multiple bone traits and the interaction among these bone traits is necessary to understand the relationship between genetic background and complex whole bone mechanical properties... - Genetic variation in mouse femoral tissue-level mineral content underlies differences in whole bone mechanical propertiesHayden 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... - Genetic variation in bone growth patterns defines adult mouse bone fragilityChristopher 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..This study provides a systematic approach, which can be applied to the human skeleton, to uncover genetic control mechanisms influencing bone fragility... - Genetic variation in the patterns of skeletal progenitor cell differentiation and progression during endochondral bone formation affects the rate of fracture healingKarl 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... - Elevated serum levels of IGF-1 are sufficient to establish normal body size and skeletal properties even in the absence of tissue IGF-1Sebastien 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... - Involvement of the Toll-like receptor 4 pathway and use of TNF-alpha antagonists for treatment of the mucopolysaccharidosesCalogera 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... - Fourier transform infrared imaging microspectroscopy and tissue-level mechanical testing reveal intraspecies variation in mouse bone mineral and matrix compositionHayden 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... - Type 2 diabetic mice demonstrate slender long bones with increased fragility secondary to increased osteoclastogenesisYuki 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... - Serum IGF-1 determines skeletal strength by regulating subperiosteal expansion and trait interactionsShoshana 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.... - A biomechanical comparison of two patterns of screw insertionSheldon 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... - Mice lacking cathepsin K maintain bone remodeling but develop bone fragility despite high bone massChao 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.... - Biological co-adaptation of morphological and composition traits contributes to mechanical functionality and skeletal fragilitySteven 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... - Phenotypic integration among trabecular and cortical bone traits establishes mechanical functionality of inbred mouse vertebraeSteven 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... - Early response to tendon fatigue damage accumulation in a novel in vivo modelDavid 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... - A syndrome of joint laxity and impaired tendon integrity in lumican- and fibromodulin-deficient miceKarl 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... - Serum complexes of insulin-like growth factor-1 modulate skeletal integrity and carbohydrate metabolismShoshana 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... - Sexual dimorphism affects tibia size and shape but not tissue-level mechanical propertiesSteven 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... - Percolation theory relates corticocancellous architecture to mechanical function in vertebrae of inbred mouse strainsSteven 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.... - Interindividual variation in functionally adapted trait sets is established during postnatal growth and predictable based on bone robustnessNirnimesh 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... - Relationship between bone morphology and bone quality in male tibias: implications for stress fracture riskSteven 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..g., military training), variation in bone quality parameters related to damageability may be a contributing factor to the increased risk of stress fracture for individuals with more slender bones... - 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-2Najmul 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... 
Cycle-dependent matrix remodeling gene expression response in fatigue-loaded rat patellar tendonsHui 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...- Subrupture tendon fatigue damageDavid 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... - Variability in tendon and knee joint biomechanics among inbred mouse strainsVincent 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... - Targeted overexpression of androgen receptor in osteoblasts: unexpected complex bone phenotype in growing animalsKristine 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... - Relationship between damage accumulation and mechanical property degradation in cortical bone: microcrack orientation is importantOzan 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... - The aging cortex: to crack or not to crackKarl J Jepsen
Osteoporos Int 14:S57-62; discussion S63-66. 2003 - The Collaborative Cross, a community resource for the genetic analysis of complex traitsGary 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... - Long-term disuse osteoporosis seems less sensitive to bisphosphonate treatment than other osteoporosisChao Yang Li
Mt Sinai Sch Med, New York, NY
J Bone Miner Res 20:117-24. 2005..Our results suggest that risedronate impairs osteoclastic function but cannot completely overcome the intense stimulus for osteoclast recruitment during prolonged disuse... - Three-dimensional reconstruction of fracture callus morphogenesisLouis 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... - The effect of recovery time and test conditions on viscoelastic measures of tensile damage in cortical boneWon 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... - 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 skeletonKristine 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 Grants
- GENETIC DETERMINATION OF SKELETAL FRAGILITYKarl 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. ..
- GENETIC DETERMINATION OF SKELETAL FRAGILITYKarl 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. ..
- GENETIC DETERMINATION OF SKELETAL FRAGILITYKarl J Jepsen; Fiscal Year: 2010....
- Functionality and Fracture Susceptibility of Corticocancellous StructuresKarl 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. ..