Mechanobiology of bone cells

Summary

Bone mass, morphology and properties of the bone material are regulated by the functions of osteoblasts, osteocytes, and osteoclasts. These cells respond directly or indirectly to mechanical forces from the environment with the expression of differentiation markers, proliferation or release of bioactive factors. Osteocytes appear to be an important regulator for the adaptation of bone to changes in the mechanical environment. Mesenchymal stem cells which are located in bone marrow can be mechanically stimulated to differentiate into osteoblasts and chondrocytes but not to adipocytes. Integrin receptors are the principal mediators of mechanical forces and induce a signal transduction. The conversion of mechanical signals into biochemical signals is facilitated by unfolding of proteins to expose binding sites. Implant materials offer the opportunity to control the mechanical stimulation of cells by modifying the rigidity, geometry of adhesion sites, and the 3D-environment.

Zusammenfassung

Knochenmasse, Morphologie und Eigenschaften des Knochens werden durch Osteoblasten, Osteozyten und Osteoklasten reguliert. Diese Zellen reagieren direkt oder indirekt auf mechanische Stimuli aus der Umgebung mit der Expression von Differenzierungsmarkern, mit Proliferation oder Freisetzung von bioaktiven Faktoren. Osteozyten sind wichtige Regulatoren für die Adaptation des Knochens an Veränderungen der mechanischen Umgebung. Mesenchymale Stammzellen, die im Knochenmark lokalisiert sind, können durch mechanische Stimulation in Osteoblasten und Chondrozyten, aber nicht in Adipozyten differenzieren. Integrinrezeptoren sind die wesentlichen Mediatoren der mechanischen Kräfte und induzieren eine Signaltransduktion. Die Umwandlung von mechanischen Signalen in biochemische Signale wird durch das Entfalten von Proteinen zur Präsentation von Bindungsstellen ermöglicht. Implantatmaterialien bieten die Möglichkeit, durch Modifikation der Steifigkeit, der geometrischen Anordnung von Adhäsionsmotiven und der Gestaltung der 3D-Umgebung die mechanische Stimulation der Zellen zu steuern.

Keywords

Bone cells - mechanics - mesenchymal stem cells - differentiation

Schlüsselwörter

Knochenzellen - Mechanik - mesenchymale Stammzellen - Differenzierung

• References

• 1 Aguirre JI, Plotkin LI, Stewart SA. et al. Osteocyte apoptosis is induced by weightlessness in mice and precedes osteoclast recruitment and bone loss. J Bone Miner Res 2006; 21: 605-615.
• 2 Antia M, Baneyx G, Kubow KE, Vogel V. Fibronectin in aging extracellular matrix fibrils is progressively unfolded by cells and elicits an enhanced rigidity response. Faraday Discuss 2008; 139: 229-249.
• 3 Arnold M, Cavalcanti-Adam EA, Glass R. et al. Activation of integrin function by nanopatterned adhesive interfaces. Chemphyschem 2004; 05: 383-388.
• 4 Baneyx G, Baugh L, Vogel V. Fibronectin extension and unfolding within cell matrix fibrils controlled by cytoskeletal tension. Proc Natl Acad Sci U S A 2002; 99: 5139-5143.
• 5 Caplan AI. Why are MSCs therapeutic? New data: new insight. J Pathol 2009; 217: 318-324.
• 6 Cartmell SH, Dobson J, Verschueren SB, El Haj AJ. Development of magnetic particle techniques for long-term culture of bone cells with intermittent mechanical activation. IEEE Trans Nanobioscience 2002; 01: 92-97.
• 7 Cavalcanti-Adam EA, Aydin D, Hirschfeld-Warneken VC, Spatz JP. Cell adhesion and response to synthetic nanopatterned environments by steering receptor clustering and spatial location. HFSP J 2008; 02: 276-285.
• 8 Chen JH, Liu C, You L, Simmons CA. Boning up on Wolff ‘s Law: mechanical regulation of the cells that make and maintain bone. J Biomech 2010; 43: 108-118.
• 9 Chowdhury F, Na S, Li D. et al. Material properties of the cell dictate stress-induced spreading and differentiation in embryonic stem cells. Nat Mater 2010; 09: 82-88.
• 10 Davidson RM, Tatakis DW, Auerbach AL. Multiple forms of mechanosensitive ion channels in osteoblast-like cells. Pflugers Arch 1990; 416: 646-651.
• 11 del Rio A, Perez-Jimenez R, Liu R. et al. Stretching single talin rod molecules activates vinculin binding. Science 2009; 323: 638-641.
• 12 Discher DE, Mooney DJ, Zandstra PW. Growth factors, matrices, and forces combine and control stem cells. Science 2009; 324: 1673-1677.
• 13 Engler AJ, Sen S, Sweeney HL, Discher DE. Matrix elasticity directs stem cell lineage specification. Cell 2006; 126: 677-689.
• 14 Fu J, Wang YK, Yang MT. et al. Mechanical regulation of cell function with geometrically modulated elastomeric substrates. Nat Methods. 2010 (Epub ahead of print)
• 15 Glogauer M, Ferrier J. A new method for application of force to cells via ferric oxide beads. Pflugers Arch 1998; 435: 320-327.
• 16 Goodship AE, Lawes TJ, Rubin CT. Low-magnitude high-frequency mechanical signals accelerate and augment endochondral bone repair: preliminary evidence of efficacy. J Orthop Res 2009; 27: 922-930.
• 17 Hughes JM, Petit MA. Biological underpinnings of Frost’s mechanostat thresholds: the important role of osteocytes. J Musculoskelet Neuronal Interact 2010; 10: 128-135.
• 18 Hynes RO. Integrins: bidirectional, allosteric signaling machines. Cell 2002; 110: 673-687.
• 19 Ingber DE. Cellular tensegrity: defining new rules of biological design that govern the cytoskeleton. J Cell Sci 1993; 104 (Pt 3): 613-627.
• 20 Jacobs CR, Temiyasathit S, Castillo AB. Osteocyte mechanobiology and pericellular mechanics. Annu Rev Biomed Eng 2010; 12: 369-400.
• 21 Jakkaraju S, Zhe X, Pan D. et al. TIPs are tensionresponsive proteins involved in myogenic versus adipogenic differentiation. Dev Cell 2005; 09: 39-49.
• 22 Judex S, Gupta S, Rubin C. Regulation of mechanical signals in bone. Orthod Craniofac Res 2009; 12: 94-104.
• 23 Kadow-Romacker A, Hoffmann JE, Duda G. et al. Effect of mechanical stimulation on osteoblastand osteoclast-like cells in vitro. Cells Tissues Organs 2009; 190: 61-68.
• 24 Kanczler JM, Sura HS, Magnay J. et al. Controlled Differentiation of Human Bone Marrow Stromal Cells Using Magnetic Nanoparticle Technology. Tissue Eng Part A. 2010 (Epub ahead of print).
• 25 Kasten A, Müller P, Bulnheim U. et al. Mechanical integrin stress and magnetic forces induce biological responses in mesenchymal stem cells which depend on environmental factors. J Cell Biochem. 2010 (in revision).
• 26 Klein-Nulend J, Helfrich MH, Sterck JG. et al. Nitric oxide response to shear stress by human bone cell cultures is endothelial nitric oxide synthase dependent. Biochem Biophys Res Commun 1998; 250: 108-114.
• 27 Lin C, Jiang X, Dai Z. et al. Sclerostin mediates bone response to mechanical unloading through antagonizing Wnt/beta-catenin signaling. J Bone Miner Res 2009; 24: 1651-1661.
• 28 Liu L, Yuan W, Wang J. Mechanisms for osteogenic differentiation of human mesenchymal stem cells induced by fluid shear stress. Biomech Model Mechanobiol. 2010 (Epub ahead of print)
• 29 Lutolf MP, Gilbert PM, Blau HM. Designing materials to direct stem-cell fate. Nature 2009; 462: 433-441.
• 30 McBeath R, Pirone DM, Nelson CM. et al. Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment. Dev Cell 2004; 06: 483-495.
• 31 Mullender M, El Haj AJ, Yang Y. et al. Mechanotransduction of bone cells in vitro: mechanobiology of bone tissue. Med Biol Eng Comput 2004; 42: 14-21.
• 32 Ozcivici E, Luu YK, Adler B. et al. Mechanical signals as anabolic agents in bone. Nat Rev Rheumatol 2010; 06: 50-59.
• 33 Pommerenke H, Schmidt C, Durr F. et al. The mode of mechanical integrin stressing controls intracellular signaling in osteoblasts. J Bone Miner Res 2002; 17: 603-611.
• 34 Pommerenke H, Schreiber E, Durr F. et al. Stimulation of integrin receptors using a magnetic drag force device induces an intracellular free calcium response. Eur J Cell Biol 1996; 70: 157-164.
• 35 Potier E, Noailly J, Ito K. Directing bone marrowderived stromal cell function with mechanics. J Biomech 2010; 43: 807-817.
• 36 Rubin J, Rubin C, Jacobs CR. Molecular pathways mediating mechanical signaling in bone. Gene 2006; 367: 1-16.
• 37 Rychly J, Pommerenke H, Durr F. et al. Analysis of spatial distributions of cellular molecules during mechanical stressing of cell surface receptors using confocal microscopy. Cell Biol Int 1998; 22: 7-12.
• 38 Scaglione S, Wendt D, Miggino S. et al. Effects of fluid flow and calcium phosphate coating on human bone marrow stromal cells cultured in a defined 2D model system. J Biomed Mater Res A 2008; 86: 411-419.
• 39 Schmidt C, Pommerenke H, Durr F, Nebe B, Rychly J. Mechanical stressing of integrin receptors induces enhanced tyrosine phosphorylation of cytoskeletally anchored proteins. J Biol Chem 1998; 273: 5081-5085.
• 40 Scott A, Khan KM, Duronio V, Hart DA. Mechanotransduction in human bone: in vitro cellular physiology that underpins bone changes with exercise. Sports Med 2008; 38: 139-160.
• 41 Sen B, Xie Z, Case N. et al. Mechanical strain inhibits adipogenesis in mesenchymal stem cells by stimulating a durable beta-catenin signal. Endocrinology 2008; 149: 6065-6075.
• 42 Simmons CA, Nikolovski J, Thornton AJ. et al. Mechanical stimulation and mitogen-activated protein kinase signaling independently regulate osteogenic differentiation and mineralization by calcifying vascular cells. J Biomech 2004; 37: 1531-1541.
• 43 Titushkin I, Cho M. Modulation of cellular mechanics during osteogenic differentiation of human mesenchymal stem cells. Biophys J 2007; 93: 3693-3702.
• 44 Vogel V, Sheetz MP. Cell fate regulation by coupling mechanical cycles to biochemical signaling pathways. Curr Opin Cell Biol 2009; 21: 38-46.
• 45 Walker LM, Publicover SJ, Preston MR. et al. Calcium-channel activation and matrix protein upregulation in bone cells in response to mechanical strain. J Cell Biochem 2000; 79: 648-661.
• 46 Wang N, Tytell JD, Ingber DE. Mechanotransduction at a distance: mechanically coupling the extracellular matrix with the nucleus. Nat Rev Mol Cell Biol 2009; 10: 75-82.
• 47 Winer JP, Janmey PA, McCormick ME, Funaki M. Bone marrow-derived human mesenchymal stem cells become quiescent on soft substrates but remain responsive to chemical or mechanical stimuli. Tissue Eng Part A 2009; 15: 147-154.
• 48 Yu HC, Wu TC, Chen MR. et al. Mechanical stretching induces osteoprotegerin in differentiating C2C12 precursor cells through noncanonical Wnt pathways. J Bone Miner Res 2010; 25: 1128-1137.
• 49 Zhao S, Zhang YK, Harris S. et al. MLO-Y4 osteocyte-like cells support osteoclast formation and activation. J Bone Miner Res 2002; 17: 2068-2079.