Nanoscale Stiffness Distribution in Bone Metastasis
Author(s)
Ludovic Richert1,
Laetitia Keller2,3,
Quentin Wagner2,3,
Fabien Bornert2,3,4,
Catherine Gros2,3,4,
Sophie Bahi2,3,4,
François Clauss2,3,4,
William Bacon2,3,4,
Philippe Clézardin5,
Nadia Benkirane-Jessel2,3,4,
Florence Fioretti2,3,4
Affiliation(s)
1 Centre National de la Recherche Scientifique (CNRS), UMR, Faculté de Pharmacie de l’Université de Strasbourg (UdS), Illkirch, France. 2 Institut National de la Santé et de la Recherche Médicale (INSERM), Osteoarticular and Dental Regenerative Nanomedicine, UMR, Faculté de Médecine de l’Université de Strasbourg and FMTS, Strasbourg, France. 3 Faculté de Chirurgie Dentaire de l’Université de Strasbourg (UdS), Strasbourg, France. 4 Hôpitaux Universitaires de Strasbourg, Strasbourg, France. 5 Institut National de la Santé et de la Recherche Médicale (INSERM), UMR, Faculté de Médecine Laënnec de l’Université Claude Bernard Lyon 1, Lyon, France.
1 Centre National de la Recherche Scientifique (CNRS), UMR, Faculté de Pharmacie de l’Université de Strasbourg (UdS), Illkirch, France. 2 Institut National de la Santé et de la Recherche Médicale (INSERM), Osteoarticular and Dental Regenerative Nanomedicine, UMR, Faculté de Médecine de l’Université de Strasbourg and FMTS, Strasbourg, France. 3 Faculté de Chirurgie Dentaire de l’Université de Strasbourg (UdS), Strasbourg, France. 4 Hôpitaux Universitaires de Strasbourg, Strasbourg, France. 5 Institut National de la Santé et de la Recherche Médicale (INSERM), UMR, Faculté de Médecine Laënnec de l’Université Claude Bernard Lyon 1, Lyon, France.
ABSTRACT
Nanomechanical heterogeneity is expected to have an effect on elasticity, injury and bone remodelling. In normal bone, we have two types of cells (osteoclasts and osteoblasts) working together to maintain existing bone. Bone cancers can produce factors that make the osteoclasts work harder. This means that more bone is destroyed than rebuilt, and leads to weakening of the affected bone. We report here the first demonstration of the nanoscale stiffness distribution in bone metastases before and after treatment of animals with the bisphosphonate Risedronate, a drug which is currently used for the treatment of bone metastases in patients with advanced cancers. The strategy used here is applicable to a wide class of biological tissues and may serve as a new reflection for biologically inspired scaffolds technologies.
Nanomechanical heterogeneity is expected to have an effect on elasticity, injury and bone remodelling. In normal bone, we have two types of cells (osteoclasts and osteoblasts) working together to maintain existing bone. Bone cancers can produce factors that make the osteoclasts work harder. This means that more bone is destroyed than rebuilt, and leads to weakening of the affected bone. We report here the first demonstration of the nanoscale stiffness distribution in bone metastases before and after treatment of animals with the bisphosphonate Risedronate, a drug which is currently used for the treatment of bone metastases in patients with advanced cancers. The strategy used here is applicable to a wide class of biological tissues and may serve as a new reflection for biologically inspired scaffolds technologies.
Cite this paper
Richert, L. , Keller, L. , Wagner, Q. , Bornert, F. , Gros, C. , Bahi, S. , Clauss, F. , Bacon, W. , Clézardin, P. , Benkirane-Jessel, N. and Fioretti, F. (2015) Nanoscale Stiffness Distribution in Bone Metastasis. World Journal of Nano Science and Engineering, 5, 219-228. doi: 10.4236/wjnse.2015.54023.
Richert, L. , Keller, L. , Wagner, Q. , Bornert, F. , Gros, C. , Bahi, S. , Clauss, F. , Bacon, W. , Clézardin, P. , Benkirane-Jessel, N. and Fioretti, F. (2015) Nanoscale Stiffness Distribution in Bone Metastasis. World Journal of Nano Science and Engineering, 5, 219-228. doi: 10.4236/wjnse.2015.54023.
References
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http://dx.doi.org/10.1016/j.canlet.2007.07.007 [4] Fantner, G.E., Hassenkam, T., Kindt, J.H., Weaver, J.C., Birkedal, H., Pechenik, L., Cutroni, J.A., Cidade, G.A., Stucky, G.D., Morse, D.E. and Hansma, P.K. (2005) Sacrificial Bonds and Hidden Length Dissipate Energy as Mineralized Fibrils Separate during Bone Fracture. Nature Materials, 4, 612-616.
http://dx.doi.org/10.1038/nmat1428 [5] Gao, H., Ji, B., Jager, I.L., Arzt, E. and Fratzl, P. (2003) Materials Become Insensitive to Flaws at Nanoscale: Lessons from Nature. Proceedings of the National Academy of Sciences of the United States of America, 100, 5597-5600.
http://dx.doi.org/10.1073/pnas.0631609100 [6] Gupta, H.S., Wagermaier, W., Zickler, G.A., Raz-Ben Aroush, D., Funari, S.S., Roschger, P., Wagner, H.D. and Fratzl, P. (2005) Nanoscale Deformation Mechanisms in Bone. Nano Letters, 5, 2108-2111.
http://dx.doi.org/10.1021/nl051584b [7] Tai, K., Ulm, F.J. and Ortiz, C. (2006) Nanogranular Origins of the Strength of Bone. Nano Letters, 6, 2520-2525.
http://dx.doi.org/10.1021/nl061877k [8] Morgan, E.F., Bayraktar, H.H. and Keaveny, T.M. (2003) Trabecular Bone Modulus-Density Relationships Depend on Anatomic Site. Journal of Biomechanics, 36, 897-904.
http://dx.doi.org/10.1016/S0021-9290(03)00071-X [9] Pope, M.H. and Outwater, J.O. (1974) Mechanical Properties of Bone as a Function of Position and Orientation. Journal of Biomechanics, 7, 61-66.
http://dx.doi.org/10.1016/0021-9290(74)90070-0 [10] Gupta, H.S., Stachewicz, U., Wagermaier, W., Roschger, P., Wagner, H.D. and Fratzl, P. (2006) Mechanical Modulation at the Lamellar Level in Osteonal Bone. Journal of Materials Research, 21, 1913-1921.
http://dx.doi.org/10.1557/jmr.2006.0234 [11] Rho, J.Y., Roy, M.E., 2nd, Tsui, T.Y. and Pharr, G.M. (1999) Elastic Properties of Microstructural Components of Human Bone Tissue as Measured by Nanoindentation. Journal of Biomedical Materials Research, 45, 48-54.
http://dx.doi.org/10.1002/(SICI)1097-4636(199904)45:1<48::AID-JBM7>3.0.CO;2-5 [12] Martin, R.B. and Burr, D.B. (1989) Structure, Function and Adaptation of Compact Bone. Raven Press, New York. [13] Balooch, G., Balooch, M., Nalla, R.K., Schilling, S., Filvaroff, E.H., Marshall, G.W., Marshall, S.J., Ritchie, R.O., Derynck, R. and Alliston, T. (2005) TGF-Beta Regulates the Mechanical Properties and Composition of Bone Matrix. Proceedings of the National Academy of Sciences of the United States of America, 102, 18813-18818.
http://dx.doi.org/10.1073/pnas.0507417102 [14] Jaasma, M.J., Bayraktar, H.H., Niebur, G.L. and Keaveny, T.M. (2002) Biomechanical Effects of Intraspecimen Variations in Tissue Modulus for Trabecular Bone. Journal of Biomechanics, 35, 237-246.
http://dx.doi.org/10.1016/S0021-9290(01)00193-2 [15] Peterlik, H., Roschger, P., Klaushofer, K. and Fratzl, P. (2006) From Brittle to Ductile Fracture of Bone. Nature Materials, 5, 52-55.
http://dx.doi.org/10.1016/S0021-9290(01)00193-2 [16] Phelps, J.B., Hubbard, G.B., Wang, X. and Agrawal, C.M. (2000) Microstructural Heterogeneity and the Fracture Toughness of Bone. Journal of Biomedical Materials Research, 51, 735-741.
http://dx.doi.org/10.1002/1097-4636(20000915)51:4<735::AID-JBM23>3.0.CO;2-G [17] Currey, J. (2005) Structural Heterogeneity in Bone: Good or Bad? Journal of Musculoskeletal & Neuronal Interactions, 5, 317. [18] Tai, K., Dao, M., Suresh, S., Palazoglu, A. and Ortiz, C. (2007) Nanoscale Heterogeneity Promotes Energy Dissipation in Bone. Nature Materials, 6, 454-462.
http://dx.doi.org/10.1038/nmat1911 [19] Engler, A.J., Richert, L., Wong, J.Y., Picart, C. and Discher, D.E. (2004) Surface Probe Measurements of the Elasticity of Sectioned Tissue, Thin Gels and Polyelectrolyte Multilayer Films: Correlations between Substrate Stiffness and Cell Adhesion. Surface Science, 570, 142-154.
http://dx.doi.org/10.1016/j.susc.2004.06.179 [20] Ehrlich, P.J. and Lanyon, L.E. (2002) Mechanical Strain and Bone Cell Function: A Review. Osteoporosis International, 13, 688-700.
http://dx.doi.org/10.1007/s001980200095 [21] You, L., Cowin, S.C., Schaffler, M.B. and Weinbaum, S. (2001) A Model for Strain Amplification in the Actin Cytoskeleton of Osteocytes Due to Fluid Drag on Pericellular Matrix. Journal of Biomechanics, 34, 1375-1386.
http://dx.doi.org/10.1016/S0021-9290(01)00107-5 [22] Peyruchaud, O., Serre, C.M., NicAmhlaoibh, R., Fournier, P. and Clezardin, P. (2003) Angiostatin Inhibits Bone Metastasis Formation in Nude Mice through a Direct Anti-Osteoclastic Activity. Journal of Biomechanics, 278, 45826-45832 [23] Cowin, S.C. (1999) Bone Poroelasticity. Journal of Biomechanics, 32, 217-238.
http://dx.doi.org/10.1016/S0021-9290(98)00161-4
[1] Boissier, S., Magnetto, S., Frappart, L., Cuzin, B., Ebetino, F.H., Delmas, P.D. and Clezardin, P. (1997) Bisphosphonates Inhibit Prostate and Breast Carcinoma Cell Adhesion to Unmineralized and Mineralized Bone Extracellular Matrices. Cancer Research, 57, 3890-3894. [2] Coleman, R.E. (2008) Risks and Benefits of Bisphosphonates. British Journal of Cancer, 98, 1736-1740.
http://dx.doi.org/10.1038/sj.bjc.6604382 [3] Stresing, V., Daubine, F., Benzaid, I., Monkkonen, H. and Clezardin, P. (2007) Bisphosphonates in Cancer Therapy. Cancer Letters, 257, 16-35.
http://dx.doi.org/10.1016/j.canlet.2007.07.007 [4] Fantner, G.E., Hassenkam, T., Kindt, J.H., Weaver, J.C., Birkedal, H., Pechenik, L., Cutroni, J.A., Cidade, G.A., Stucky, G.D., Morse, D.E. and Hansma, P.K. (2005) Sacrificial Bonds and Hidden Length Dissipate Energy as Mineralized Fibrils Separate during Bone Fracture. Nature Materials, 4, 612-616.
http://dx.doi.org/10.1038/nmat1428 [5] Gao, H., Ji, B., Jager, I.L., Arzt, E. and Fratzl, P. (2003) Materials Become Insensitive to Flaws at Nanoscale: Lessons from Nature. Proceedings of the National Academy of Sciences of the United States of America, 100, 5597-5600.
http://dx.doi.org/10.1073/pnas.0631609100 [6] Gupta, H.S., Wagermaier, W., Zickler, G.A., Raz-Ben Aroush, D., Funari, S.S., Roschger, P., Wagner, H.D. and Fratzl, P. (2005) Nanoscale Deformation Mechanisms in Bone. Nano Letters, 5, 2108-2111.
http://dx.doi.org/10.1021/nl051584b [7] Tai, K., Ulm, F.J. and Ortiz, C. (2006) Nanogranular Origins of the Strength of Bone. Nano Letters, 6, 2520-2525.
http://dx.doi.org/10.1021/nl061877k [8] Morgan, E.F., Bayraktar, H.H. and Keaveny, T.M. (2003) Trabecular Bone Modulus-Density Relationships Depend on Anatomic Site. Journal of Biomechanics, 36, 897-904.
http://dx.doi.org/10.1016/S0021-9290(03)00071-X [9] Pope, M.H. and Outwater, J.O. (1974) Mechanical Properties of Bone as a Function of Position and Orientation. Journal of Biomechanics, 7, 61-66.
http://dx.doi.org/10.1016/0021-9290(74)90070-0 [10] Gupta, H.S., Stachewicz, U., Wagermaier, W., Roschger, P., Wagner, H.D. and Fratzl, P. (2006) Mechanical Modulation at the Lamellar Level in Osteonal Bone. Journal of Materials Research, 21, 1913-1921.
http://dx.doi.org/10.1557/jmr.2006.0234 [11] Rho, J.Y., Roy, M.E., 2nd, Tsui, T.Y. and Pharr, G.M. (1999) Elastic Properties of Microstructural Components of Human Bone Tissue as Measured by Nanoindentation. Journal of Biomedical Materials Research, 45, 48-54.
http://dx.doi.org/10.1002/(SICI)1097-4636(199904)45:1<48::AID-JBM7>3.0.CO;2-5 [12] Martin, R.B. and Burr, D.B. (1989) Structure, Function and Adaptation of Compact Bone. Raven Press, New York. [13] Balooch, G., Balooch, M., Nalla, R.K., Schilling, S., Filvaroff, E.H., Marshall, G.W., Marshall, S.J., Ritchie, R.O., Derynck, R. and Alliston, T. (2005) TGF-Beta Regulates the Mechanical Properties and Composition of Bone Matrix. Proceedings of the National Academy of Sciences of the United States of America, 102, 18813-18818.
http://dx.doi.org/10.1073/pnas.0507417102 [14] Jaasma, M.J., Bayraktar, H.H., Niebur, G.L. and Keaveny, T.M. (2002) Biomechanical Effects of Intraspecimen Variations in Tissue Modulus for Trabecular Bone. Journal of Biomechanics, 35, 237-246.
http://dx.doi.org/10.1016/S0021-9290(01)00193-2 [15] Peterlik, H., Roschger, P., Klaushofer, K. and Fratzl, P. (2006) From Brittle to Ductile Fracture of Bone. Nature Materials, 5, 52-55.
http://dx.doi.org/10.1016/S0021-9290(01)00193-2 [16] Phelps, J.B., Hubbard, G.B., Wang, X. and Agrawal, C.M. (2000) Microstructural Heterogeneity and the Fracture Toughness of Bone. Journal of Biomedical Materials Research, 51, 735-741.
http://dx.doi.org/10.1002/1097-4636(20000915)51:4<735::AID-JBM23>3.0.CO;2-G [17] Currey, J. (2005) Structural Heterogeneity in Bone: Good or Bad? Journal of Musculoskeletal & Neuronal Interactions, 5, 317. [18] Tai, K., Dao, M., Suresh, S., Palazoglu, A. and Ortiz, C. (2007) Nanoscale Heterogeneity Promotes Energy Dissipation in Bone. Nature Materials, 6, 454-462.
http://dx.doi.org/10.1038/nmat1911 [19] Engler, A.J., Richert, L., Wong, J.Y., Picart, C. and Discher, D.E. (2004) Surface Probe Measurements of the Elasticity of Sectioned Tissue, Thin Gels and Polyelectrolyte Multilayer Films: Correlations between Substrate Stiffness and Cell Adhesion. Surface Science, 570, 142-154.
http://dx.doi.org/10.1016/j.susc.2004.06.179 [20] Ehrlich, P.J. and Lanyon, L.E. (2002) Mechanical Strain and Bone Cell Function: A Review. Osteoporosis International, 13, 688-700.
http://dx.doi.org/10.1007/s001980200095 [21] You, L., Cowin, S.C., Schaffler, M.B. and Weinbaum, S. (2001) A Model for Strain Amplification in the Actin Cytoskeleton of Osteocytes Due to Fluid Drag on Pericellular Matrix. Journal of Biomechanics, 34, 1375-1386.
http://dx.doi.org/10.1016/S0021-9290(01)00107-5 [22] Peyruchaud, O., Serre, C.M., NicAmhlaoibh, R., Fournier, P. and Clezardin, P. (2003) Angiostatin Inhibits Bone Metastasis Formation in Nude Mice through a Direct Anti-Osteoclastic Activity. Journal of Biomechanics, 278, 45826-45832 [23] Cowin, S.C. (1999) Bone Poroelasticity. Journal of Biomechanics, 32, 217-238.
http://dx.doi.org/10.1016/S0021-9290(98)00161-4