Home

Modulation Of Bone´s Mechanical Behavior By Bone Quality

Stefan Judex, Assistant Professor
Biomedical Engineeringstate University New York Stony Brook

Grant 5R01AR052778-02 from National Institute Of Arthritis And Musculoskeletal And Skin Diseases, IRG: SBSR

Abstract: The strength of bone is a product of the quantity and quality of the tissue. We propose that the compromise in bone strength that cannot be fully explained by a decrease in bone quantity is propagated by inherent defects in the material, resulting in an increased susceptibility to fracture. Similarly, antiresorptive (e.g., bisphosphonates) and anabolic (e.g., PTH) treatments for musculoskeletal diseases may influence both the quantity and quality of the bone matrix, and thus can ultimately improve (or compromise) bone´s ability to resist load, but the manner in which this is achieved remains unclear. The underlying hypothesis of this proposal is that subtle modulation of bone´s matrix properties, as manifested in chemical composition (e.g., mineral/matrix ratio, calcium/phosphorus ratio, collagen structure, crystallinity) and/or structure will markedly influence the quality of bone, and will result in direct effects on bone structural behavior under mechanical load (e.g., bone stiffness, strength, resilience, toughness). Using a unique combination of state of the art chemical, mechanical, morphological, and histological assays, the primary aim of this study is to identify the principal matrix and architectural factors that define bone quality. These relations will be derived from the rat skeleton defined through aging as well as in situations when the remodeling balance is altered (withdrawal of estrogen) and treated with anti-catabolic or anabolic treatments. These conditions will establish a large range of microscopic and macroscopic tissue properties which will be quantified by in situ synchrotron infrared microspectroscopy and small-angle x-ray scattering to determine chemical properties, synchrotron nano-CT and micro-CT to determine the structure, and nano-indentation and macroscopic mechanical testing regimes to determine mechanical properties. Taken together, these systematic studies present a unique opportunity to first identify and then test precise interrelationships between biochemical, mechanical, and structural factors during aging, hormonal imbalances, and anti-catabolic/anabolic treatment at different hierarchical levels. Identification of these potential chemical targets will provide critical information for improved diagnostic, prophylactic, and therapeutic means of addressing bone quality defects induced by aging, disease, and treatment. The strength of bone is a not only related to the quantity of the tissue but also to its quality. In this project, we will determine the specific material components that determine the mechanic quality of bone. Identification of these potential chemical targets will provide critical information for improved diagnostic, prophylactic, and therapeutic means of addressing bone quality defects in disease

Project start date: 2007-09-15

Project end date: 2011-08-31


Sponsored Links Lab Supply Mall http://www.labsupplymall.com

Qiagen Ni-NTA Agarose beads 25 ml Cat # 30210
For purification of 6xHis-tagged proteins by gravity-flow chromatography. $225, $180
Invitrogen NuPAGE Novex 4-12% Bis-Tris Gels
Best resolution and most consistent results,long shelf-life - at least 8 months! . $117.5, $95
Invitrogen Human Cot-1 DNA Cat# 15279-011
Block non-specific hybridization in microarray screening. $155, $120
Amersham ECL Plus Western Blotting Detection Reagents, Cat # RPN2132
Superior sensitivity.. $230, $55
Invitrogen Life Technology Gibo Lipofectamine 2000, 1.5 ml, Cat 11668-019
Unsurpassed Results for DNA and siRNA Transfections. $399, $350
Qiagen QIAEX II Gel Extraction Kit (150), Cat # 20021
For batch purification of DNA fragments (40 bp to 50 kb) from agarose gels and from solutions. $137, $105
Qiagen Plasmid Maxi Kit (25), Cat # 12163
For purification of up to 500 ug transfection grade plasmid or cosmid DNA. $454, $395
New Invitrogen UltraPure Agarose 500g
UltraPure Agarose resolves DNA and RNA fragments from 100 bp to >30 kb. $432, $350
QIAGEN Plasmid Maxi Kit (10), Cat # 12162
For purification of up to 500 ug transfection grade plasmid or cosmid DNA. $192, $150
GR Safe Nucleic Acid Stain
Excellent Alternative to Ethidium Bromide: Safety, Sensitivity, Stability. $78, $58


Grants awarded to Stefan Judex

Modulation Of Bone´s Mechanical Behavior By Bone Quality

Stefan Judex, Assistant Professor
Biomedical Engineeringstate University New York Stony Brook

Grant 5R01AR052778-02 from National Institute Of Arthritis And Musculoskeletal And Skin Diseases, IRG: SBSR

Abstract: The strength of bone is a product of the quantity and quality of the tissue. We propose that the compromise in bone strength that cannot be fully explained by a decrease in bone quantity is propagated by inherent defects in the material, resulting in an increased susceptibility to fracture. Similarly, antiresorptive (e.g., bisphosphonates) and anabolic (e.g., PTH) treatments for musculoskeletal diseases may influence both the quantity and quality of the bone matrix, and thus can ultimately improve (or compromise) bone´s ability to resist load, but the manner in which this is achieved remains unclear. The underlying hypothesis of this proposal is that subtle modulation of bone´s matrix properties, as manifested in chemical composition (e.g., mineral/matrix ratio, calcium/phosphorus ratio, collagen structure, crystallinity) and/or structure will markedly influence the quality of bone, and will result in direct effects on bone structural behavior under mechanical load (e.g., bone stiffness, strength, resilience, toughness). Using a unique combination of state of the art chemical, mechanical, morphological, and histological assays, the primary aim of this study is to identify the principal matrix and architectural factors that define bone quality. These relations will be derived from the rat skeleton defined through aging as well as in situations when the remodeling balance is altered (withdrawal of estrogen) and treated with anti-catabolic or anabolic treatments. These conditions will establish a large range of microscopic and macroscopic tissue properties which will be quantified by in situ synchrotron infrared microspectroscopy and small-angle x-ray scattering to determine chemical properties, synchrotron nano-CT and micro-CT to determine the structure, and nano-indentation and macroscopic mechanical testing regimes to determine mechanical properties. Taken together, these systematic studies present a unique opportunity to first identify and then test precise interrelationships between biochemical, mechanical, and structural factors during aging, hormonal imbalances, and anti-catabolic/anabolic treatment at different hierarchical levels. Identification of these potential chemical targets will provide critical information for improved diagnostic, prophylactic, and therapeutic means of addressing bone quality defects induced by aging, disease, and treatment. The strength of bone is a not only related to the quantity of the tissue but also to its quality. In this project, we will determine the specific material components that determine the mechanic quality of bone. Identification of these potential chemical targets will provide critical information for improved diagnostic, prophylactic, and therapeutic means of addressing bone quality defects in disease

Project start date: 2007-09-15

Project end date: 2011-08-31


1R01AR052778-01A2 (2007): $311774


Related Publications

Hwang SJ, Lublinsky S, Seo YK, Kim IS, Judex S.
Abstract Extremely Small-magnitude Accelerations Enhance Bone Regeneration: A Preliminary Study. Clin Orthop Relat Res. 2008 Oct 15. [Epub ahead of print] PMID: 18855088

Lublinsky S, Luu YK, Rubin CT, Judex S.
Abstract Automated Separation of Visceral and Subcutaneous Adiposity in In Vivo Microcomputed Tomographies of Mice. J Digit Imaging. 2008 Sep 3. [Epub ahead of print] PMID: 18769966

Ozcivici E, Ferreri S, Qin YX, Judex S.
Abstract Determination of bone's mechanical matrix properties by nanoindentation. Methods Mol Biol. 2008; 455: 323-34. PMID: 18463828

Xie L, Rubin C, Judex S.
Abstract Enhancement of the adolescent murine musculoskeletal system using low-level mechanical vibrations. J Appl Physiol. 2008 Apr; 104( 4): 1056-62. Epub 2008 Feb 7. PMID: 18258802

Squire M, Brazin A, Keng Y, Judex S.
Abstract Baseline bone morphometry and cellular activity modulate the degree of bone loss in the appendicular skeleton during disuse. Bone. 2008 Feb; 42( 2): 341-9. Epub 2007 Oct 2. PMID: 17997144

Chen X, Macica C, Nasiri A, Judex S, Broadus AE.
Free in PMC Mechanical regulation of PTHrP expression in entheses. Bone. 2007 Nov; 41( 5): 752-9. Epub 2007 Aug 11. PMID: 17869201

Lublinsky S, Ozcivici E, Judex S.
Abstract An automated algorithm to detect the trabecular-cortical bone interface in micro-computed tomographic images. Calcif Tissue Int. 2007 Oct; 81( 4): 285-93. Epub 2007 Sep 9. PMID: 17828460

Carlson KJ, Judex S.
Free Full Text Increased non-linear locomotion alters diaphyseal bone shape. J Exp Biol. 2007 Sep; 210( Pt 17): 3117-25. PMID: 17704086

Ozcivici E, Garman R, Judex S.
Abstract High-frequency oscillatory motions enhance the simulated mechanical properties of non-weight bearing trabecular bone. J Biomech. 2007; 40( 15): 3404-11. Epub 2007 Jul 25. PMID: 17655852

Garman R, Rubin C, Judex S.
Free in PMC Small oscillatory accelerations, independent of matrix deformations, increase osteoblast activity and enhance bone morphology. PLoS ONE. 2007 Jul 25; 2( 7): e653. PMID: 17653280 [PubMed]
Bastie CC, Zong H, Xu J, Busa B, Judex S, Kurland IJ, Pessin JE.
Abstract Integrative metabolic regulation of peripheral tissue fatty acid oxidation by the SRC kinase family member Fyn. Cell Metab. 2007 May; 5( 5): 371-81. PMID: 17488639

Miller LM, Little W, Schirmer A, Sheik F, Busa B, Judex S.
Abstract Accretion of bone quantity and quality in the developing mouse skeleton. J Bone Miner Res. 2007 Jul; 22( 7): 1037-45. PMID: 17402847

Garman R, Gaudette G, Donahue LR, Rubin C, Judex S.
Abstract Low-level accelerations applied in the absence of weight bearing can enhance trabecular bone formation. J Orthop Res. 2007 Jun; 25( 6): 732-40. PMID: 17318899

Gilsanz V, Wren TA, Sanchez M, Dorey F, Judex S, Rubin C.
Abstract Low-level, high-frequency mechanical signals enhance musculoskeletal development of young women with low BMD. J Bone Miner Res. 2006 Sep; 21( 9): 1464-74. PMID: 16939405

Rubin C, Judex S, Qin YX.
Free Full Text Low-level mechanical signals and their potential as a non-pharmacological intervention for osteoporosis. Age Ageing. 2006 Sep; 35 Suppl 2: ii32-ii36. PMID: 16926201

Xie L, Jacobson JM, Choi ES, Busa B, Donahue LR, Miller LM, Rubin CT, Judex S.
Abstract Low-level mechanical vibrations can influence bone resorption and bone formation in the growing skeleton. Bone. 2006 Nov; 39( 5): 1059-66. Epub 2006 Jul 7. PMID: 16824816

Judex S, Lei X, Han D, Rubin C.
Abstract Low-magnitude mechanical signals that stimulate bone formation in the ovariectomized rat are dependent on the applied frequency but not on the strain magnitude. J Biomech. 2007; 40( 6): 1333-9. Epub 2006 Jun 30. PMID: 16814792

Judex S, Boyd S, Qin YX, Miller L, Müller R, Rubin C.
Abstract Combining high-resolution micro-computed tomography with material composition to define the quality of bone tissue. Curr Osteoporos Rep. 2003 Jun; 1( 1): 11-9. Review. PMID: 16036060

Zhong N, Garman RA, Squire ME, Donahue LR, Rubin CT, Hadjiargyrou M, Judex S.
Abstract Gene expression patterns in bone after 4 days of hind-limb unloading in two inbred strains of mice. Aviat Space Environ Med. 2005 Jun; 76( 6): 530-5. PMID: 15945395

Murfee WL, Hammett LA, Evans C, Xie L, Squire M, Rubin C, Judex S, Skalak TC.
Free Full Text High-frequency, low-magnitude vibrations suppress the number of blood vessels per muscle fiber in mouse soleus muscle. J Appl Physiol. 2005 Jun; 98( 6): 2376-80. Epub 2005 Jan 27. PMID: 15677735