Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure on bone material properties

Finnilä, Mikko A. J.; Zioupos, Peter; Herlin, Maria; Miettinen, Hanna; Simanainen, Ulla; Håkansson, Helen; Tuukkanen, Juha; Viluksela, Matti; Jämsä, Timo

doi:10.1016/j.jbiomech.2009.12.011

Cited by 48 publications

(41 citation statements)

References 31 publications

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“…Nanoindentations were performed using a G200 nanoindenter (Agilent Technologies) fitted with a Berkovich shaped diamond tip having a Poisson ratio of 0.07 and elastic modulus of 114 GPa. The indenter was controlled with Testworks 4 version 4.10 (MTS System Corporation) to produce 60 indentations using both quasistatic and dynamic loading schemes [34]. Indentations for tibiae were done in the anterior-medial aspect of the transverse diaphyseal bone, while indentations in the femur were done on an anterior section.…”

Section: Methodsmentioning

confidence: 99%

PHOSPHO1 is essential for mechanically competent mineralization and the avoidance of spontaneous fractures

Huesa

Yadav

Finnilä

et al. 2011

Bone

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Phosphatases are essential for the mineralization of the extracellular matrix within the skeleton. Their precise identities and functions however remain unclear. PHOSPHO1 is a phosphoethanolamine/phosphocholine phosphatase involved in the generation of inorganic phosphate for bone mineralization. It is highly expressed at sites of mineralization in bone and cartilage. The bones of Phospho1−/− mice are hypomineralized, bowed and present with spontaneous greenstick fractures at birth. In this study we show that PHOSPHO1 is essential for mechanically competent mineralization that is able to withstand habitual load. Long bones from Phospho1−/− mice did not fracture during 3- point bending but deformed plastically. With dynamic loading nanoindentation the elastic modulus and hardness of Phospho1−/− tibiae were significantly lower than wild-type tibia. Raman microscopy revealed significantly lower mineral:matrix ratios and lower carbonate substitutions in Phospho1−/− tibia. The altered dihydroxylysinonorleucine/hydroxyllysinonorleucine and pyridoline/deoxypyridinoline collagen crosslink ratios indicated possible changes in lysyl hydroxylase-1 activity and/or bone mineralization status. The bone formation and resorption markers, N-terminal propeptide and C-terminal telopeptide of Type I collagen, were both increased in Phospho1−/− mice and this we associated with increased bone remodelling during fracture repair or an attempt to remodel a mechanically competent bone capable of withstanding physiological load. In summary these data indicate that Phospho1−/− bones are hypomineralized and, consequently, are softer and more flexible. An inability to withstand physiological loading may explain the deformations noted. We hypothesize that this phenotype is due to the reduced availability of inorganic phosphate to form hydroxyapatite during mineralization, creating an undermineralized yet active bone.

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Section: Methodsmentioning

confidence: 99%

PHOSPHO1 is essential for mechanically competent mineralization and the avoidance of spontaneous fractures

Huesa

Yadav

Finnilä

et al. 2011

Bone

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“…49 The storage modulus and loss modulus of bone decreased, whereas the loss tangent increased with decreasing bone mineral contents. 50 Les et al reported that the storage modulus of bone was positively correlated with its mineralization extent, whereas the loss tangent was negatively correlated with its mineralization.…”

Section: Mechanical Properties Of Cells/hydrogel Constructmentioning

confidence: 97%

Osteogenic Differentiation and Ectopic Bone Formation of Canine Bone Marrow-Derived Mesenchymal Stem Cells in Injectable Thermo-Responsive Polymer Hydrogel

Liao

Chen

2011

Tissue Engineering Part C: Methods

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This study describes an injectable, thermo-responsive hyaluronic acid-g-chitosan-g-poly(N-isopropylacrylamide) (HA-CPN) copolymer for bone tissue engineering. The wettability, temperature-dependent change of water content, and volume of HA-CPN hydrogel were measured, together with its biocompatibility in vitro and in vivo. The dried hydrogel morphology shows a three-dimensional, porous structure with interconnected pores. Canine bone marrow-derived mesenchymal stem cells (cBMSCs) were encapsulated in HA-CPN hydrogel and osteoinduction was assessed by comparing samples with different osteogenic differentiation induction times but with the same total cell culture time. Cell proliferation and time-dependent osteogenic differentiation, evident from secretion of extracellular matrix and formation of mineral deposits, were observed. The cells showed better proliferation in HA-CPN hydrogel than on tissue culture polystyrene after osteo-induced for 21 days and higher alkaline phosphatase activity regardless of osteo-induction times. Mineralization extent of cBMSCs in HA-CPN followed by Alizarin red stains showed positive stained nodules after osteo-induced longer than 7 days. The cells/hydrogel construct also showed increased mechanical strength and elasticity after osteogenic differentiation, and the increase could be correlated with osteo-induction time. In vivo studies confirmed the biocompatibility and bioresorption of the HA-CPN hydrogel and ectopic bone formation when the hydrogel was used as a cell carrier for osteo-induced cBMSCs and implanted in nude mice subcutaneously. Taken together, the results indicate the feasibility and efficacy of HA-CPN hydrogel as an injectable bone tissue engineering scaffold with cBMSCs.

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“…The most detailed toxicological bone studies were performed with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the organohalogen pollutant model compound, which exerts most of its effects through activation of the aryl hydrocarbon receptor (AhR) (Denison and Nagy 2003;Herlin et al 2010;Jämsä et al 2001). In utero and lactational exposure to TCDD alters bone geometry, mineral density, and biomechanical strength in rat offspring (Miettinen et al 2005;Finnilä et al 2010), and retards bone maturation patterns at the bone matrix level (Finnilä et al 2010).…”

Section: Perinatal Exposure To Environmental Contaminants Detected Inmentioning

confidence: 99%

Perinatal Exposure to Environmental Contaminants Detected in Canadian Arctic Human Populations Changes Bone Geometry and Biomechanical Properties in Rat Offspring

Elabbas

Finnilä

Herlin

et al. 2011

Journal of Toxicology and Environmental Health, Part A

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Arctic inhabitants consume large proportions of fish and marine mammals, and are therefore continuously exposed to levels of environmental toxicants, which may produce adverse health effects. Fetuses and newborns are the most vulnerable groups. The aim of this study was to evaluate changes in bone geometry, mineral density, and biomechanical properties during development following perinatal exposure to a mixture of environmental contaminants corresponding to maternal blood levels in Canadian Arctic human populations. Sprague-Dawley rat dams were dosed with a Northern Contaminant Mixture (NCM) from gestational day 1 to postnatal day (PND) 23. NCM contains 27 contaminants comprising polychlorinated biphenyls, organochlorine pesticides, and methylmercury. Femurs were collected on PND 35, 77 and 350, and diaphysis was analyzed by peripheral quantitative computed tomography and three-point bending test, while femoral neck was assessed in an axial loading experiment. Dose-response modeling was performed to establish the benchmark dose (BMD) for the analyzed bone parameters. Exposure to the high dose of NMC resulted in short and thin femur with reduced mechanical strength in offspring at PND35. BMD of femur length, cortical area, and stiffness were 3.2, 1.6, and 0.8 mg/kg bw/d, respectively. At PND77 femur was still thin, but at PND350 no treatment-related bone differences were detected. This study provides new insights on environmental contaminants present in the maternal blood of Canadian Arctic populations, showing that perinatal exposure induces bone alterations in the young offspring. These findings could be significant from a health risk assessment point of view.

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Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure on bone material properties

Cited by 48 publications

References 31 publications

PHOSPHO1 is essential for mechanically competent mineralization and the avoidance of spontaneous fractures

PHOSPHO1 is essential for mechanically competent mineralization and the avoidance of spontaneous fractures

Osteogenic Differentiation and Ectopic Bone Formation of Canine Bone Marrow-Derived Mesenchymal Stem Cells in Injectable Thermo-Responsive Polymer Hydrogel

Perinatal Exposure to Environmental Contaminants Detected in Canadian Arctic Human Populations Changes Bone Geometry and Biomechanical Properties in Rat Offspring

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