Cancellous Bone Properties and Matrix Content of TGF-beta2 and IGF-I in Human Tibia: a Pilot Study

Overview

Journal Clin Orthop Relat Res

Publisher Wolters Kluwer

Specialty Orthopedics

Date 2009 May 28

PMID 19472023

Citations 5

Authors

Yener N Yeni

X Neil Dong

Bingbing Zhang

Gary J Gibson

David P Fyhrie

Affiliations

Soon will be listed here.

Abstract

Transforming and insulin-like growth factors are important in regulating bone mass. Thus, one would anticipate correlations between matrix concentrations of growth factors and functional properties of bone. We therefore investigated the relationships of (1) TGF-beta2 and (2) IGF-I matrix concentrations with the trabecular microstructure, stress distribution, and mechanical properties of tibial cancellous bone from six male human cadavers. Trabecular stress amplification (VMExp/sigma(app)) and variability (VMCOV) were calculated using microcomputed tomography (muCT)-based finite element simulations. Bone volume fraction (BV/TV), surface/volume ratio (BS/BV), trabecular thickness (Tb.Th), number (Tb.N) and separation (Tb.Sp), connectivity (Eu.N), and anisotropy (DA) were measured using 3-D morphometry. Bone stiffness and strength were measured by mechanical testing. Matrix concentrations of TGF-beta2 and IGF-I were measured by ELISA. We found higher matrix concentrations of TGF-beta2 were associated with higher Tb.Sp and VMExp/sigma(app) for pooled data and within subjects. Similarly, a higher matrix concentration of IGF-I was associated with lower stiffness, strength, BV/TV and Tb.Th and with higher BS/BV, Tb.Sp, VMExp/sigma(app) and VMCOV for pooled data and within subjects. IGF-I and Tb.N were negatively associated within subjects. It appears variations of the stress distribution in cancellous bone correlate with the variation of the concentrations of TGF-beta2 and IGF-I in bone matrix: increased local matrix concentrations of growth factors are associated with poor biomechanical and architectural properties of tibial cancellous bone.

Citing Articles

Atypical histological presentation of bone regeneration after insertion of cryoprotected allogeneic bone graft.

Cruz P, Bortoli J, Benalcazar-Jalkh E, Boutros S, Bhola M, Grande F Med Oral Patol Oral Cir Bucal. 2023; 29(1):e103-e110.

PMID: 37992144 PMC: 10765327. DOI: 10.4317/medoral.26094.

Assessing Bone Mineral Density in Weight-Bearing Regions of the Body through Texture Analysis of Abdomen and Pelvis CT Hounsfield Unit.

Kim M, Huh J, Noh Y, Seo H, Lee D Diagnostics (Basel). 2023; 13(18).

PMID: 37761335 PMC: 10529497. DOI: 10.3390/diagnostics13182968.

THE MEASUREMENT OF BONE QUALITY USING GRAY LEVEL CO-OCCURRENCE MATRIX TEXTURAL FEATURES.

Shirvaikar M, Huang N, Dong X J Med Imaging Health Inform. 2017; 6(6):1357-1362.

PMID: 28042512 PMC: 5198780. DOI: 10.1166/jmihi.2016.1812.

Assessment of bone fragility with clinical imaging modalities.

Dong X, Wang X Hard Tissue. 2013; 2(1):7.

PMID: 24294491 PMC: 3840397. DOI: 10.13172/2050-2303-2-1-351.

Biomechanical properties and microarchitecture parameters of trabecular bone are correlated with stochastic measures of 2D projection images.

Dong X, Shirvaikar M, Wang X Bone. 2013; 56(2):327-36.

PMID: 23756232 PMC: 3755113. DOI: 10.1016/j.bone.2013.05.023.

References

Ding M . Age variations in the properties of human tibial trabecular bone and cartilage. Acta Orthop Scand Suppl. 2000; 292:1-45. DOI: 10.1080/000164700753749791. View

Malpe R, Baylink D, Linkhart T, Wergedal J, Mohan S . Insulin-like growth factor (IGF)-I, -II, IGF binding proteins (IGFBP)-3, -4, and -5 levels in the conditioned media of normal human bone cells are skeletal site-dependent. J Bone Miner Res. 1997; 12(3):423-30. DOI: 10.1359/jbmr.1997.12.3.423. View

Balooch G, Balooch M, Nalla R, Schilling S, Filvaroff E, Marshall G . TGF-beta regulates the mechanical properties and composition of bone matrix. Proc Natl Acad Sci U S A. 2005; 102(52):18813-8. PMC: 1323171. DOI: 10.1073/pnas.0507417102. View

Hildebrand T, Laib A, Muller R, Dequeker J, Ruegsegger P . Direct three-dimensional morphometric analysis of human cancellous bone: microstructural data from spine, femur, iliac crest, and calcaneus. J Bone Miner Res. 1999; 14(7):1167-74. DOI: 10.1359/jbmr.1999.14.7.1167. View

Gingery A, Bradley E, Pederson L, Ruan M, Horwood N, Oursler M . TGF-beta coordinately activates TAK1/MEK/AKT/NFkB and SMAD pathways to promote osteoclast survival. Exp Cell Res. 2008; 314(15):2725-38. PMC: 2578840. DOI: 10.1016/j.yexcr.2008.06.006. View

Nakasaki M, Yoshioka K, Miyamoto Y, Sasaki T, Yoshikawa H, Itoh K . IGF-I secreted by osteoblasts acts as a potent chemotactic factor for osteoblasts. Bone. 2008; 43(5):869-79. DOI: 10.1016/j.bone.2008.07.241. View

Rivadeneira F, Houwing-Duistermaat J, Beck T, Janssen J, Hofman A, Pols H . The influence of an insulin-like growth factor I gene promoter polymorphism on hip bone geometry and the risk of nonvertebral fracture in the elderly: the Rotterdam Study. J Bone Miner Res. 2004; 19(8):1280-90. DOI: 10.1359/JBMR.040405. View

Okazaki R, Durham S, Riggs B, Conover C . Transforming growth factor-beta and forskolin increase all classes of insulin-like growth factor-I transcripts in normal human osteoblast-like cells. Biochem Biophys Res Commun. 1995; 207(3):963-70. DOI: 10.1006/bbrc.1995.1279. View

Triplett J, ORiley R, Tekulve K, Norvell S, Pavalko F . Mechanical loading by fluid shear stress enhances IGF-1 receptor signaling in osteoblasts in a PKCzeta-dependent manner. Mol Cell Biomech. 2007; 4(1):13-25. View

10.

Fyhrie D, Hoshaw S, Hamid M, Hou F . Shear stress distribution in the trabeculae of human vertebral bone. Ann Biomed Eng. 2001; 28(10):1194-9. DOI: 10.1114/1.1318928. View

11.

Yeni Y, Hou F, Vashishth D, Fyhrie D . Trabecular shear stress in human vertebral cancellous bone: intra- and inter-individual variations. J Biomech. 2001; 34(10):1341-6. DOI: 10.1016/s0021-9290(01)00089-6. View

12.

Chenu C, Pfeilschifter J, Mundy G, Roodman G . Transforming growth factor beta inhibits formation of osteoclast-like cells in long-term human marrow cultures. Proc Natl Acad Sci U S A. 1988; 85(15):5683-7. PMC: 281824. DOI: 10.1073/pnas.85.15.5683. View

13.

Erlebacher A, Derynck R . Increased expression of TGF-beta 2 in osteoblasts results in an osteoporosis-like phenotype. J Cell Biol. 1996; 132(1-2):195-210. PMC: 2120709. DOI: 10.1083/jcb.132.1.195. View

14.

Goulet R, Goldstein S, Ciarelli M, Kuhn J, Brown M, Feldkamp L . The relationship between the structural and orthogonal compressive properties of trabecular bone. J Biomech. 1994; 27(4):375-89. DOI: 10.1016/0021-9290(94)90014-0. View

15.

Fiorelli G, Formigli L, Zecchi Orlandini S, Gori F, Falchetti A, Morelli A . Characterization and function of the receptor for IGF-I in human preosteoclastic cells. Bone. 1996; 18(3):269-76. DOI: 10.1016/8756-3282(95)00485-8. View

16.

Langdahl B, Kassem M, Moller M, Eriksen E . The effects of IGF-I and IGF-II on proliferation and differentiation of human osteoblasts and interactions with growth hormone. Eur J Clin Invest. 1998; 28(3):176-83. DOI: 10.1046/j.1365-2362.1998.00265.x. View

17.

Hill P, Reynolds J, Meikle M . Osteoblasts mediate insulin-like growth factor-I and -II stimulation of osteoclast formation and function. Endocrinology. 1995; 136(1):124-31. DOI: 10.1210/endo.136.1.7828521. View

18.

Bikle D . Integrins, insulin like growth factors, and the skeletal response to load. Osteoporos Int. 2008; 19(9):1237-46. PMC: 9005159. DOI: 10.1007/s00198-008-0597-z. View

19.

Reijnders C, Bravenboer N, Tromp A, Blankenstein M, Lips P . Effect of mechanical loading on insulin-like growth factor-I gene expression in rat tibia. J Endocrinol. 2007; 192(1):131-40. DOI: 10.1677/joe.1.06880. View

20.

Boonen S, Aerssens J, Dequeker J, Nicholson P, Cheng X, Lowet G . Age-associated decline in human femoral neck cortical and trabecular content of insulin-like growth factor I: potential implications for age-related (type II) osteoporotic fracture occurrence. Calcif Tissue Int. 1997; 61(3):173-8. DOI: 10.1007/s002239900318. View