Bone response to in vivo mechanical loading in two breeds of mice

wbldb

Akhter, M. P.¹; Cullen, D. M.¹; Pedersen, E. A.¹; Kimmel, D. B.¹; Recker, R. R.¹

Bone response to in vivo mechanical loading in two breeds of mice

Calcif Tiss Int. November 1998;63(5):442-449

©1998 Springer-Verlag New York Inc.

Affiliations

¹Osteoporosis Research Center, Creighton University, 601 North 30th Street 5766, Omaha, Nebraska 68131, USA
Abstract and keywords

We investigated the bone response to external loading in C57BL/6J and C3H/HeJ mice, both breeds with low and high bone density, respectively. An in vivo tibial four-point bending device previously used for application of measured external loads in rats was adapted for mice. It delivered a uniform medio-lateral bending moment to the region of the tibia located 1–5.5 mm proximal to the tibio-fibula junction. The right legs of six C57BL/6J [low bone density (LBD)] and C3H/HeJ [high bone density (HBD)] mice were externally loaded in the device for 36 cycles/day at 2 Hz, 6 days/week for 2 weeks at 9.3 ± 0.9 N force, inducing estimated lateral periosteal surface compressive strains of 5121 ± 1128 με in C3H/HeJ (HBD) mice (n = 6), significantly higher than the estimated 3988 ± 820 με in C57BL/6J mice (n = 6) (mean ± SD). In addition, C3H/HeJ HBD mice (n = 11) were externally sham (pad pressure or no bending) loaded in the device for 36 cycles/day at 2 Hz, 3 days/week for 3 weeks at 9.3 ± 0.9 N force. Calcein injections for bone labeling were given at the 10th and 3rd days before sacrifice. At the end of the experiment, all mice were killed and both tibiae were removed, fixed, embedded, and cross-sectioned through the loaded region. Both tibiae were measured for marrow area (Ma.Ar), cortical area (Ct.Ar), total area (Tt.Ar), cross-sectional moment of inertia (CSMI), and periosteal and endocortical woven bone surface (Wo.B/BS), single-labeled surface (sLS), double-labeled surface (dLS), and total formation surface (FS/BS). Differences in all variables due to breed and loading (both bending and sham-bending) were tested by two-way analysis of variance (ANOVA) (P < 0.05). Ma.Ar, Tt.Ar, and CSMI were greater in C57BL/6J (LBD) than in C3H/HeJ (HBD) mice. Periosteal and endocortical woven bone and formation surface were increased significantly more by loading (bending) in C57BL/6J than in C3H/HeJ mice. Periosteal woven bone response due to sham-bending or sham-loading was significantly lower than due to bending loads in the C3H/HeJ mice. We conclude that the bone response to external loading is greater in LBD mice than in HBD mice. The high bone density of C3H/HeJ (HBD) mice is related to breed-specific factors other than the response to loading.

Keywords: In vivo strain; External loading; Fourpoint bending; Tibia
Links

DOI: 10.1007/s002239900554

PubMed: 9799831

WoS: 000076464900014
History

Received: 1997-03-05

Accepted: 1998-04-08

Cited Works (27)

Year	Entry
1989	Keller TS, Spengler DM. Regulation of bone stress and strain in the immature and mature rat femur. J Biomech. 1989;22(11-12):1115-1127.
1991	Gärdsell P, Johnell O, Nilsson BE. The predictive value of bone loss for fragility fractures in women: a longitudinal study over 15 years. Calcif Tiss Int. August 1991;49(2):90-94.
1979	Goodship AE, Lanyon LE, McFie H. Functional adaptation of bone to increased stress: an experimental study. J Bone Joint Surg. June 1979;61A(4):539-546.
1989	Burr DB, Schaffler MB, Yang KH, Wu DD, Lukoschek M, Kandzari D, Sivaneri N, Blaha JD, Radin EL. The effects of altered strain environments on bone tissue kinetics. Bone. 1989;10(3):215-221.
1994	Torrance AG, Mosley JR, Suswillo RFL, Lanyon LE. Noninvasive loading of the rat ulna in vivo induces a strain-related modeling response uncomplicated by trauma or periostal pressure. Calcif Tiss Int. March 1994;54(3):241-247.
1992	Akhter MP, Raab DM, Turner CH, Kimmel DB, Recker RR. Characterization of in vivo strain in the rat tibia during external application of a four-point bending load. J Biomech. October 1992;25(10):1241-1246.
1996	Beamer WG, Donahue LR, Rosen CJ, Baylink DJ. Genetic variability in adult bone density among inbred strains of mice. Bone. May 1996;18(5):397-403.
1996	Duey P, Desbois C, Boyce B, Pinerot G, Story B, Dunstan C, Smith E, Bonadioll J, Goldstein S, Gundberg C, Bradley A, Karsenty G. Increased bone formation in osteocalcin-deficient mice. Nature. August 1, 1996;382(6590):448-452.
1993	Chambers TJ, Evans M, Gardner TN, Turner-Smith A, Chow JWM. Induction of bone formation in rat tail vertebrae by mechanical loading. Bone Miner. February 1993;20(2):167-178.
1973	Smith DM, Nance WE, Kang KW, Christian JC, Johnston CC Jr. Genetic factors in determining bone mass. J Clin Invest. 1973;52(11):2800-2808.
1972	Cochran GVB. Implantation of strain gages on bone in vivo. J Biomech. January 1972;5(1):119-123.
1991	Turner CH, Akhter MP, Raab DM, Kimmel DB, Recker RR. A noninvasive, in vivo model for studying strain adaptive bone modeling. Bone. 1991;12(2):73-79.
1989	Hui SL, Slemenda CW, Johnston CC Jr. Baseline measurement of bone mass predicts fracture in white women. Ann Intern Med. September 1, 1989;111(5):355-361.
1982	Lanyon LE, Goodship AE, Pye CJ, MacFie JH. Mechanically adaptive bone remodelling. J Biomech. 1982;15(3):141-154.
1989	Gärdsell P, Johnell O, Nilsson BE. Predicting fractures in women by using forearm bone densitometry. Calcif Tiss Int. April 1989;44(4):235-242.
1983	Baron R, Vignery A, Neff L, Silvergate A, Santa Maria A. Processing of undecalcified bone specimens for bone histomorphometry. In: Recker RR, ed. Bone Histomorphometry: Techniques and Interpretation. Boca Raton, FL: Inc., CRC Press; 1983:13-35.
1969	Seireg A, Kempke W. Behavior of in vivo bone under cyclic loading. J Biomech. October 1969;2(4):455-461.
1992	Snow-Harter C, Bouxsein ML, Lewis BT, Carter DR, Marcus R. Effects of resistance and endurance exercise on bone mineral status of young women: a randomized exercise intervention trial. J Bone Miner Res. July 1992;7(7):761-769.
1985	Rubin CT, Lanyon LE. Regulation of bone mass by mechanical strain magnitude. Calcif Tiss Int. 1985;37(4):411-417.
1984	Rubin CT, Lanyon LE. Regulation of bone formation by applied dynamic loads. J Bone Joint Surg. March 1984;66A(3):397-402.
1992	Black DM, Cummings SR, Genant HK, Nevitt MC, Palermo L, Browner W. Axial and appendicular bone density predict fractures in older women. J Bone Miner Res. June 1992;7(6):633-638.
1994	Turner CH, Forwood MR, Rho J, Yoshikawa T. Mechanical loading thresholds for lamellar and woven bone formation. J Bone Miner Res. January 1994;9(1):87-97.
1990	Bonadio J, Saunders TL, Tsai E, Goldstein SA, Morris-Wiman J, Brinkley L, Dolan DF, Altschuler RA, Hawkins JE Jr, Bateman JF, Mascara T, Jaenisch R. Transgenic mouse model of the mild dominant form of osteogenesis imperfecta. Proc Natl Acad Sci USA. September 1990;87(18):7145-7149.
1991	Slemenda CW, Christian JC, Williams CJ, Norton JA, Johnston CC Jr. Genetic determinants of bone mass in adult women: a reevaluation of the twin model and the potential importance of gene interaction on heritability estimates. J Bone Miner Res. June 1991;6(6):561-567.
1988	Dalsky GP, Stocke KS, Ehsani AA, Slatopolsky E, Lee WC, Birge SJ Jr. Weight-bearing exercise training and lumbar bone mineral content in postmenopausal women. Ann Intern Med. June 1988;108(6):824-828.
1982	O'Connor JA, Lanyon LE, MacFie H. The influence of strain rate on adaptive bone remodelling. J Biomech. 1982;15(10):767-781.
1976	Burstein AH, Reilly DT, Martens M. Aging of bone tissue: mechanical properties. J Bone Joint Surg. 1976;58A(1):82-86.

Cited By (51)

Year	Entry
2002	Currey JD. Bones: Structure and Mechanics. Princeton, NJ: Princeton University Press; 2002.
1999	Sheng MH-C, Baylink DJ, Beamer WG, Donahue LR, Rosen CJ, Lau K-HW, Wergedal JE. Histomorphometric studies show that bone formation and bone mineral apposition rates are greater in C3H/HeJ (high-density) than C57BL/6J (low-density) mice during growth. Bone. October 1999;25(4):421-429.
2001	van der Meulen MCH, Jepsen KJ, Mikić B. Understanding bone strength: size isn’t everything. Bone. July 2001;29(1):101-104.
2002	Lee KCL, Maxwell A, Lanyon LE. Validation of a technique for studying functional adaptation of the mouse ulna in response to mechanical loading. Bone. September 2002;31(3):407-412.
2005	Fritton JC, Myers ER, Wright TM, van der Meulen MCH. Loading induces site-specific increases in mineral content assessed by microcomputed tomography of the mouse tibia. Bone. June 2005;36(6):1030-1038.
2006	van der Meulen MCH, Morgan TG, Yang X, Baldini TH, Myers ER, Wright TM, Bostrom MPG. Cancellous bone adaptation to in vivo loading in a rabbit model. Bone. June 2006;38(6):871-877.
2007	Wallace JM, Rajachar RM, Allen MR, Bloomfield SA, Robey PG, Young MF, Kohn DH. Exercise-induced changes in the cortical bone of growing mice are bone- and gender-specific. Bone. April 2007;40(4):1120-1127.
2010	Sugiyama T, Price JS, Lanyon LE. Functional adaptation to mechanical loading in both cortical and cancellous bone is controlled locally and is confined to the loaded bones. Bone. February 2010;46(2):314-321.
2021	Metzger CE, Swallow EA, Stacy AJ, Allen MR. Strain-specific alterations in the skeletal response to adenine-induced chronic kidney disease are associated with differences in parathyroid hormone levels. Bone. July 2021;148:115963.
2000	Kodama Y, Umemura Y, Nagasawa S, Beamer WG, Donahue LR, Rosen CR, Baylink DJ, Farley JR. Exercise and mechanical loading increase periosteal bone formation and whole bone strength in C57BL/6J mice but not in C3H/Hej mice. Calcif Tiss Int. April 2000;66(4):298-306.
2000	Akhter MP, Iwaniec UT, Covey MA, Cullen DM, Kimmel DB, Recker RR. Genetic variations in bone density, histomorphometry, and strength in mice. Calcif Tiss Int. October 2000;67(4):337-344.
2002	Judex S, Donahue L, Rubin C. Genetic predisposition to low bone mass is paralleled by an enhanced sensitivity to signals anabolic to the skeleton. FASEB J. August 2002;16(10):1280-1282.
2002	Morey-Holton ER, Globus RK. Hindlimb unloading rodent model: technical aspects. J Appl Physiol. April 2002;92(4):1367-1377.
2006	Robinson JA, Chatterjee-Kishore M, Yaworsky PJ, Cullen DM, Zhao W, Li C, Kharode Y, Sauter L, Babij P, Brown EL, Hill AA, Akhter MP, Johnson ML, Recker RR, Komm BS, Bex FJ. Wnt/β-catenin signaling is a normal physiological response to mechanical loading in bone. J Biol Chem. October 20, 2006;281(42):31720-31728.
2002	van der Meulen MC, Huiskes R. Why mechanobiology? a survey article. J Biomech. April 2002;35(4):401-414.
2002	Gross TS, Srinivasan S, Liu CC, Clemens TL, Bain SD. Noninvasive loading of the murine tibia: an in vivo model for the study of mechanotransduction. J Bone Miner Res. March 2002;17(3):493-501.
2004	Judex S, Garman R, Squire M, Busa B, Donahue L-R, Rubin C. Genetically linked site-specificity of disuse osteoporosis. J Bone Miner Res. April 2004;19(4):607-613.
2005	Bouxsein ML, Myers KS, Shultz KL, Donahue LR, Rosen CJ, Beamer WG. Ovariectomy‐induced bone loss varies among inbred strains of mice. J Bone Miner Res. July 2005;20(7):1085-1092.
2005	Price C, Herman BC, Lufkin T, Goldman HM, Jepsen KJ. Genetic variation in bone growth patterns defines adult mouse bone fragility. J Bone Miner Res. November 2005;20(11):1983-1991.
2007	Schneider P, Stauber M, Voide R, Stampanoni M, Donahue LR, Müller R. Ultrastructural properties in cortical bone vary greatly in two inbred strains of mice as assessed by synchrotron light based micro‐ and nano‐CT. J Bone Miner Res. October 2007;22(10):1557-1570.
2008	Fritton JC, Myers ER, Wright TM, van der Meulen MCH. Bone mass is preserved and cancellous architecture altered due to cyclic loading of the mouse tibia after orchidectomy. J Bone Miner Res. May 2008;23(5):663-671.
2009	Wallace JM, Golcuk K, Morris MD, Kohn DH. Inbred strain-specific response to biglycan deficiency in the cortical bone of C57BL6/129 and C3H/He mice. J Bone Miner Res. June 2009;24(6):1002-1012.
2003	Jepsen KJ, Akkus OJ, Majeska RJ, Nadeau JH. Hierarchical relationship between bone traits and mechanical properties in inbred mice. Mamm Genome. February 2003;14(2):97-104.
2002	Ehrlich PJ, Lanyon LE. Mechanical strain and bone cell function: a review. Osteoporos Int. September 2002;13(9):688-700.
2017	Saers JPP. Ontogeny and Functional Adaptation of Trabecular Bone in the Human Foot [PhD thesis]. Cambridge, UK: University of Cambridge; July 2017.
2011	Maranjian KJ. Mechanical and Material Property Changes in Bone With Experimental Diabetes: A Murine Model [Master's thesis]. Boulder, CO: University of Colorado; 2011.
2006	Fritton JC. Mechanical Loading Induced Adaptation of the Mouse Tibia [PhD thesis]. Ithaca, NY: Cornell University; January 2006.
2010	Lynch ME. Cancellous Bone Adaptation to Non-Invasive Mechanical Loading in the Murine Tibia [PhD thesis]. Ithaca, NY: Cornell University; August 2010.
2022	Chlebek C. Identification of Novel Cellular Pathways Involved in Bone Mechanotransduction Using Transcriptomics [PhD thesis]. Ithaca, NY: Cornell University; May 2022.
2009	Wang Y. Roles of Integrins in Flow Induced Mechanotransduction in Osteocytes [PhD thesis]. New York, NY: The City University of New York; 2009.
2011	Donaldson FE. On Incorporating Bone Microstructure in Macro-Finite-Element Models [PhD thesis]. Edinburgh, UK: University of Edinburgh; March 2011.
2007	Schneider P. Ultrastructural Phenotyping of Murine Bone Using Synchrotron Micro- and Nano-Computed Tomography [PhD thesis]. Swiss Federal Institute of Technology Zürich; 2007.
2007	Voide R. Functional Phenotyping of Bone: A Hierarchical Assessment of Bone Failure Characteristics [PhD thesis]. Swiss Federal Institute of Technology Zürich; 2007.
2008	Webster DJ. A Combined Experimental and Computational Model for Genetic Control of Micro Structural Bone Adaptation [PhD thesis]. Swiss Federal Institute of Technology Zürich; 2008.
2011	Rigozzi S. Structure and Function in Tendon: Experimental Studies on the Ultrastructural Determinants of Tendon Biomechanical Function [PhD thesis]. Swiss Federal Institute of Technology Zürich; 2011.
2021	Yan C. Tibial Bone Properties and Mechanics Under Atypical Loading Conditions [PhD thesis]. University of Illinois at Urbana-Champaign; 2021.
2011	Moodie J. Destabilisation of the Medial Meniscus: Imaging and Mechanics of a Murine Surgical Osteoarthritis Model [PhD thesis]. Imperial College London; August 2011.
2023	Ren T. Mechanoregulation of Bone Fracture Healing in the Tibia from the Perspective of Computational Models and Image Analysis [PhD thesis]. Lehigh University; January 2023.
2008	Price C. Systems Based Approaches to Identifying How Genetically Varying Skeletal Growth Affects Skeletal Functionality and Fragility [PhD thesis]. Mount Sinai School of Medicine; 2008.
2019	Mustafy T. The Short and Long Term Effects of in Vivo Cyclic Axial Compression Applied During Puberty on Bone Growth, Morphometry and Biomechanics [PhD thesis]. École polytechnique de Montréal; July 2019.
2010	Gurkan UA. Engineering of Bone Marrow in Vitro for Investigating the Role of Growth Factors and Their Mechanoresponsiveness in Osteogenesis [PhD thesis]. Purdue University; May 2010.
2016	Berman AG. Influence of Mechanical Stimulation on the Quantity and Quality of Bone During Modeling [Master's thesis]. Purdue University; August 2016.
2018	Samvelyan H. The Effect of Timing of Feeding on Bone's Adaptive Response to Mechanical Loading [PhD thesis]. University of Sheffield; March 2018.
2012	Khayyeri H. Computational Investigations of Variability in Mechanobiological Simulations of Tissue Differentiation [PhD thesis]. Trinity College Dublin; 2012.
2004	Castillo AB. The Female Ferret (Mustela Putorius Furo) as an in Vivo Model for Skeletal Research [PhD thesis]. Davis, University of California; 2004.
2020	Caffrey JP. Experimental Biomechanics of Musculoskeletal Injury Models and Repair Implants [PhD thesis]. San Diego (UCSD), University of California; 2020.
2007	Wallace JM III. Investigating the Inbred Strain-Specific Response to Biglycan-Deficiency and Exercise: A Study in Genetically-Mediated Skeletal Adaptation [PhD thesis]. University of Michigan; 2007.
2021	Li Y. Adaptation of Maternal Skeletal Mechano-Responsiveness, Osteocyte Microenvironment, and Bone Marrow Adipocytes in Response to Reproduction and Lactation [PhD thesis]. Philadelphia, PA: University of Pennsylvania; 2021.
2016	Collins CJ. A Comprehensive Evaluation of Methods to Determine Mechanical Properties of Long Bone [PhD thesis]. University of Wisconsin – Madison; 2016.
2016	Meyer LA. Testing and Modeling Mechanical Properties of Ex Vivo Trabecular Bone [PhD thesis]. University of Wisconsin – Madison; 2016.
2009	McKenzie JA. Investigations Into the Ulnar Response to Mechanical Stimuli Activating Lamellar and Woven Bone Formation [PhD thesis]. St. Louis, MO: Washington University in St. Louis; December 2009.