Skip to main content

Advertisement

Log in

Stress amplification during development of the tendon-to-bone attachment

  • Original Paper
  • Published:
Biomechanics and Modeling in Mechanobiology Aims and scope Submit manuscript

Abstract

Mechanical stress is necessary to sustain the mineral content of bone in adults. However, in a developing neonatal mouse, the mineralization of soft tissues progresses despite greatly reduced average mechanical stresses. In adults, these reduced loads would likely lead to bone loss. Although biochemical factors may partly explain these different responses, it is unclear how mineralization is initiated in low load environments. We present here the effect of morphometric data and initial modeling supporting a hypothesis that mechanical factors across several length scales amplify stresses, and we suggest that these stresses are of a level adequate to contribute to mechanical signaling for initiation of mineralization at the developing tendon-to-bone enthesis. A mineral gradient is evident across the insertion from the onset of mineralization. This grading maintains a constant size from early postnatal time points to adulthood. At the tissue level, this grading contributes to reduced stresses in an adult animal and to a minor elevation of stresses in a neonatal animal. At the cellular level, stress concentrations around mineralizing chondrocytes are enhanced in neonatal animals compared with adult animals. The enhancement of stresses around cells at early time points may serve to amplify and transduce low loads in order to initiate mineralization.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

References

  • Adams SL, Pallante KM, Pacifici M (1989) Effects of cell shape type x collagen gene expression in hypertrophic chondrocytes. Connect Tissue Res 20(1–4):223–232

    Article  Google Scholar 

  • Alexander B, Daulton TL, Genin GM, Lipner J, Pasteris JD, Wopenka B, Thomopoulos S (2012) The nanometre-scale physiology of bone: steric modelling and scanning transmission electron microscopy of collagen-mineral structure. J R Soc Interface 9(73):1774–1786

    Google Scholar 

  • Alexopoulos LG, Williams GM, Upton ML, Setton LA, Guilak F (2005) Osteoarthritic changes in the biphasic mechanical properties of the chondrocyte pericellular matrix in articular cartilage. J Biomech 38(3):509–517

    Article  Google Scholar 

  • Amiel D, Woo SLY, Harwood FL, Akeson WH (1982) The effect of immobilization on collagen turnover in connective tissue: a biochemical-biomechanical correlation. Acta Orthop 53(3):325–332

    Article  Google Scholar 

  • Bailey DA, McKay HA, Mirwald RL, Crocker PRE, Faulkner RA (1999) A six-year longitudinal study of the relationship of physical activity to bone mineral accrual in growing children: the university of saskatchewan bone mineral accrual study. J Bone Miner Res 14(10):1672–1679

    Article  Google Scholar 

  • Benjamin M, Kumai T, Milz S, Boszczyk BM, Boszczyk AA, Ralphs JR (2002) The skeletal attachment of tendons-tendon “entheses”. Comp Biochem Phys A 133(4):931–945

    Article  Google Scholar 

  • Benjamin M, Toumi H, Ralphs JR, Bydder G, Best TM, Milz S (2006) Where tendons and ligaments meet bone: attachment sites (’entheses’) in relation to exercise and/or mechanical load. J Anat 208(4):471–490

    Article  Google Scholar 

  • Blitz E, Viukov S, Sharir A, Shwartz Y, Galloway JL, Pryce BA, Johnson RL, Tabin CJ, Schweitzer R, Zelzer E (2009) Bone ridge patterning during musculoskeletal assembly is mediated through scx regulation of bmp4 at the tendon-skeleton junction. Dev Cell 17(6):861–873

    Article  Google Scholar 

  • Burkholder TJ, Fingado B, Baron S, Lieber RL (1994) Relationship between muscle fiber types and sizes and muscle architectural properties in the mouse hindlimb. J Morphol 221(2):177–190

    Article  Google Scholar 

  • Chayes F (1956) Petrographic modal analysis: an elementary statistical appraisal. Wiley, New York

    Google Scholar 

  • Coe MR, Summers TA, Parsons SJ, Boskey AL, Balian G (1992) Matrix mineralization in hypertrophic chondrocyte cultures: beta glycerophosphate increases type x collagen messenger RNA and the specific activity of pp60c-src kinase. Bone Miner 18(2):91–106

    Article  Google Scholar 

  • Collet PH, Uebelhart D, Vico L, Moro L, Hartmann D, Roth M, Alexandre C (1997) Effects of 1-and 6-month spaceflight on bone mass and biochemistry in two humans. Bone 20(6):547–551

    Article  Google Scholar 

  • Delesse A (1847) Precede mechanique pour determines la composition de roches (extrait). CR Acad Sci (Paris) 25:544–560

    Google Scholar 

  • Galatz LM, Ball CM, Teefey SA, Middleton WD, Yamaguchi K (2004) The outcome and repair integrity of completely arthroscopically repaired large and massive rotator cuff tears. J Bone Joint Surg Am 86(2):219–224

    Google Scholar 

  • Galatz LM, Charlton N, Das R, Kim HM, Havlioglu N, Thomopoulos S (2009) Complete removal of load is detrimental to rotator cuff healing. J Should Elb Surg 18(5):669–675

    Article  Google Scholar 

  • Genin GM, Birman V (2009) Micromechanics and structural response of functionally graded, particulate-matrix, fiber-reinforced composites. Int J Solids Struct 46(10):2136–2150

    Article  MATH  Google Scholar 

  • Genin GM, Kent A, Birman V, Wopenka B, Pasteris JD, Marquez PJ, Thomopoulos S (2009) Functional grading of mineral and collagen in the attachment of tendon to bone. Biophys J 97(4):976–985

    Article  Google Scholar 

  • Gokhin DS, Ward SR, Bremner SN, Lieber RL (2008) Quantitative analysis of neonatal skeletal muscle functional improvement in the mouse. J Exp Biol 211(6):837–843

    Article  Google Scholar 

  • Guilak F, Ratcliffe A, Mow VC (1995) Chondrocyte deformation and local tissue strain in articular cartilage: a confocal microscopy study. J Orthop Res 13(3):410–421

    Article  Google Scholar 

  • Hall BK (2005) Bones and cartilage: developmental and evolutionary skeletal biology. Academic Press, Waltham

  • Harryman DT, Mack LA, Wang KY, Jackins SE, Richardson ML, Matsen FA (1991) Repairs of the rotator cuff. correlation of functional results with integrity of the cuff. J Bone Joint Surg Am 73:982–989

    Google Scholar 

  • Jones WR, Ping Ting-Beall H (1999) Alterations in the Youngs modulus and volumetric properties of chondrocytes isolated from normal and osteoarthritic human cartilage. J Biomech 32(2):119–127

    Article  Google Scholar 

  • Kaplan FS, Hayes WC, Keaveny TM, Boskey A, Einhorn TA, Iannotti JP (1994) Form and function of bone. In: Simon SP (ed) Orthopaedic basic science. American Academy Orthopedic Surgeons, Columbus, OH, pp 127–185

  • Kim E, Guilak F, Haider MA (2010) An axisymmetric boundary element model for determination of articular cartilage pericellular matrix properties in situ via inverse analysis of chondron deformation. J Biomech Eng 132(031):011

    Google Scholar 

  • Liu Y, Thomopoulos S, Chen C, Birman V, Buehler MJ, Genin GM (2014) Modelling the mechanics of partially mineralized collagen fibrils, fibres and tissue. J R Soc Interface 11:20130835

    Google Scholar 

  • Liu YX, Birman V, Chen CQ, Thomopoulos S, Genin GM (2011) Mechanisms of bimaterial attachment at the interface of tendon to bone. J Eng Mater Technol Trans ASME 133(011):006

    Google Scholar 

  • Liu YX, Thomopoulos S, Birman V, Li JS, Genin GM (2012) Bi-material attachment through a compliant interfacial system at the tendon-to-bone insertion site. Mech Mater 44:83–92

    Article  Google Scholar 

  • Liu Z, Lavine KJ, Hung IH, Ornitz DM (2007) Fgf18 is required for early chondrocyte proliferation, hypertrophy and vascular invasion of the growth plate. Dev Biol 302(1):80–91

    Article  Google Scholar 

  • Lui PPY, Zhang P, Chan KM, Qin L (2010) Biology and augmentation of tendon-bone insertion repair. J Orthop Surg Res 5(1):1–14

    Article  Google Scholar 

  • Lynch HA, Johannessen W, Wu JP, Jawa A, Elliott DM (2003) Effect of fiber orientation and strain rate on the nonlinear uniaxial tensile material properties of tendon. J Biomech Eng 125:726–731

    Article  Google Scholar 

  • Maganaris CN, Paul JP (1999) In vivo human tendon mechanical properties. J Physiol 521(1):307–313

    Article  Google Scholar 

  • Marquez J, Genin G, Zahalak G, Elson E (2005) The relationship between cell and tissue strain in three-dimensional bio-artificial tissues. Biophys J 88(2):778–789

    Article  Google Scholar 

  • Marquez J, Genin G, Pryse K, Elson E (2006) Cellular and matrix contributions to tissue construct stiffness increase with cellular concentration. Ann Biomed Eng 34(9):1475–1482

    Article  Google Scholar 

  • Marquez J, Elson E, Genin G (2010) Whole cell mechanics of contractile fibroblasts: relations between effective cellular and extracellular matrix moduli. Philos Trans R Soc A Math Phys Eng Sci 368(1912):635–654

    Article  Google Scholar 

  • Nekouzadeh A, Pryse K, Elson E, Genin G (2007) A simplified approach to quasi-linear viscoelastic modeling. J Biomech 40(14):3070–3078

    Article  Google Scholar 

  • Nowlan NC, Murphy P, Prendergast PJ (2008) A dynamic pattern of mechanical stimulation promotes ossification in avian embryonic long bones. J Biomech 41(2):249–258

    Article  Google Scholar 

  • Nowlan NC, Sharpe J, Roddy KA, Prendergast PJ, Murphy P (2010) Mechanobiology of embryonic skeletal development: insights from animal models. Birth Defects Res Part C Embryo Today Rev 90(3):203–213

    Article  Google Scholar 

  • Nowlan NC, Dumas G, Tajbakhsh S, Prendergast PJ, Murphy P (2012) Biophysical stimuli induced by passive movements compensate for lack of skeletal muscle during embryonic skeletogenesis. Biomech Model Mechanobiol 11(1–2):207–219

    Article  Google Scholar 

  • Pryse K, Nekouzadeh A, Genin G, Elson E, Zahalak G (2003) Incremental mechanics of collagen gels: new experiments and a new viscoelastic model. Ann Biomed Eng 31(10):1287–1296

    Article  Google Scholar 

  • Qiu H, Zhu Y, Sun Z, Trzeciakowski J, Gansner M, Depre C, Resuello R, Natividad F, Hunter W, Genin G et al (2010) Vascular smooth muscle cell stiffness as a mechanism for increased aortic stiffness with agingnovelty and significance. Circ Res 107(5):615–619

    Article  Google Scholar 

  • Schwartz A, Pasteris JD, Genin GM, Daulton T, Thomopoulos S (2012) The nanometer-scale physiology of bone: steric modeling and scanning transmission electron microscopy of collagen-mineral structure. PLoS ONE 7(11):e48630

    Google Scholar 

  • Smith L, Xia Y, Galatz L, Genin G, Thomopoulos S (2012) Tissue-engineering strategies for the tendon/ligament-to-bone insertion. Connect Tissue Res 53(2):95–105

    Article  Google Scholar 

  • Stabile KJ, Pfaeffle J, Weiss JA, Fischer K, Tomaino MM (2004) Bi-directional mechanical properties of the human forearm interosseous ligament. J Orthop Res 22(3):607–612

    Article  Google Scholar 

  • Stokes IAF (2002) Mechanical effects on skeletal growth. J Musculoskelet Neuron Interact 2(3):277–280

    Google Scholar 

  • Stokes IAF, Mente PL, Iatridis JC, Farnum CE, Aronsson DD (2002) Growth plate chondrocyte enlargement modulated by mechanical loading. Stud Health Technol Inform 88:378–381

    Google Scholar 

  • Tanck E, Hannink G, Ruimerman R, Buma P, Burger EH, Huiskes R (2006) Cortical bone development under the growth plate is regulated by mechanical load transfer. J Anat 208(1):73–79

    Article  Google Scholar 

  • Thomopoulos S, Williams GR, Gimbel JA, Favata M, Soslowsky LJ (2003) Variation of biomechanical, structural, and compositional properties along the tendon to bone insertion site. J Orth Res 21(3):413–419

    Article  Google Scholar 

  • Thomopoulos S, Marquez J, Weinberger B, Birman V, Genin G (2006) Collagen fiber orientation at the tendon to bone insertion and its influence on stress concentrations. J Biomech 39(10):1842–1851

    Article  Google Scholar 

  • Thomopoulos S, Kim HM, Rothermich SY, Biederstadt C, Das R, Galatz LM (2007) Decreased muscle loading delays maturation of the tendon enthesis during postnatal development. J Orth Res 25(9):1154–1163

    Article  Google Scholar 

  • Thomopoulos S, Genin GM, Galatz LM (2010) The development and morphogenesis of the tendon-to-bone insertion-what development can teach us about healing. J Musculoskelet Neuronal Interact 10(1):35–45

    Google Scholar 

  • Thomopoulos S, Das R, Birman V, Smith L, Ku K, Elson E, Pryse K, Marquez J, Genin G (2011) Fibrocartilage tissue engineering: the role of the stress environment on cell morphology and matrix expression. Tissue Eng Part A 17(7–8):1039–1053

    Article  Google Scholar 

  • Weiss JA, Gardiner JC, Bonifasi-Lista C (2002) Ligament material behavior is nonlinear, viscoelastic and rate-independent under shear loading. J Biomech 35(7):943–950

    Article  Google Scholar 

  • Woo SL, Gomez MA, Woo YK, Akeson WH (1982) Mechanical properties of tendons and ligaments. ii. the relationships of immobilization and exercise on tissue remodeling. Biorheology 19(3):397

    Google Scholar 

  • Wopenka B, Kent A, Pasteris JD, Yoon Y, Thomopoulos S (2008) The tendon-to-bone transition of the rotator cuff: a preliminary raman spectroscopic study documenting the gradual mineralization across the insertion in rat tissue samples. Appl Spectrosc 62(12):1285–1294

    Article  Google Scholar 

  • Yagami K, Suh JY, Enomoto-Iwamoto M, Koyama E, Abrams WR, Shapiro IM, Pacifici M, Iwamoto M (1999) Matrix GLA protein is a developmental regulator of chondrocyte mineralization and, when constitutively expressed, blocks endochondral and intramembranous ossification in the limb. J Cell Biol 147(5):1097

    Article  Google Scholar 

  • Yin L, Elliott DM (2004) A biphasic and transversely isotropic mechanical model for tendon: application to mouse tail fascicles in uniaxial tension. J Biomech 37(6):907–916

    Article  Google Scholar 

Download references

Acknowledgments

This work was supported in part by the NSF (CAREER 844607), by the NIH ( R01 AR055580 ) , by a joint NIH-NSF grant (U01EB016422 ) , and by the Washington University Musculoskeletal Research Center (NIH P30 AR057235). YXL acknowledges a graduate fellowship from the Fannie Stevens Murphy foundation and AGS from the NIH (T32 AR060719). The authors thank Sandra Matteucci and Lynnea Brumbaugh for assistance with manuscript preparation.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Guy M. Genin.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (pdf 215 KB)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Liu, Y., Schwartz, A.G., Birman, V. et al. Stress amplification during development of the tendon-to-bone attachment. Biomech Model Mechanobiol 13, 973–983 (2014). https://doi.org/10.1007/s10237-013-0548-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10237-013-0548-2

Keywords

Navigation