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Roland Chapurlat - One of the best experts on this subject based on the ideXlab platform.
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Determinants of microdamage in elderly human vertebral trabecular bone.
PloS one, 2013Co-Authors: Hélène Follet, Evelyne Gineyts, Pierre D Delmas, Brigitte Burt-pichat, Stéphanie Viguet-carrin, Yohann Bala, Georges Boivin, Delphine Farlay, Julien Wegrzyn, Roland ChapurlatAbstract:Previous studies have shown that microdamage accumulates in bone as a result of physiological loading and occurs naturally in human trabecular bone. The purpose of this study was to determine the factors associated with pre-existing microdamage in human vertebral trabecular bone, namely age, architecture, hardness, mineral and organic matrix. Trabecular bone cores were collected from human L2 vertebrae (n = 53) from donors 54-95 years of age (22 men and 30 women, 1 unknown) and previous cited parameters were evaluated. Collagen Cross-Link content (PYD, DPD, PEN and % of Collagen) was measured on surrounding trabecular bone. We found that determinants of microdamage were mostly the age of donors, architecture, mineral characteristics and mature enzymatic Cross-Links. Moreover, linear microcracks were mostly associated with the bone matrix characteristics whereas diffuse damage was associated with architecture. We conclude that linear and diffuse types of microdamage seemed to have different determinants, with age being critical for both types.
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Effects of preexisting microdamage, Collagen Cross-Links, degree of mineralization, age, and architecture on compressive mechanical properties of elderly human vertebral trabecular bone.
Journal of Orthopaedic Research, 2011Co-Authors: Hélène Follet, Evelyne Gineyts, Brigitte Burt-pichat, Stéphanie Viguet-carrin, Baptiste Dépalle, Yohann Bala, Françoise Munoz, Monique Arlot, Georges Boivin, Roland ChapurlatAbstract:Previous studies have shown that the mechanical properties of trabecular bone are determined by bone volume fraction (BV/TV) and microarchitecture. The purpose of this study was to explore other possible determinants of the mechanical properties of vertebral trabecular bone, namely Collagen Cross-Link content, microdamage, and mineralization. Trabecular bone cores were collected from human L2 vertebrae (n = 49) from recently deceased donors 54-95 years of age (21 men and 27 women). Two trabecular cores were obtained from each vertebra, one for preexisting microdamage and mineralization measurements, and one for BV/TV and quasi-static compression tests. Collagen Cross-Link content (PYD, DPD, and PEN) was measured on surrounding trabecular bone. Advancing age was associated with impaired mechanical properties, and with increased microdamage, even after adjustment by BV/TV. BV/TV was the strongest determinant of elastic modulus and ultimate strength (r² = 0.44 and 0.55, respectively). Microdamage, mineralization parameters, and Collagen Cross-Link content were not associated with mechanical properties. These data indicate that the compressive strength of human vertebral trabecular bone is primarily determined by the amount of trabecular bone, and notably unaffected by normal variation in other factors, such as Cross-Link profile, microdamage and mineralization.
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effects of preexisting microdamage Collagen cross links degree of mineralization age and architecture on compressive mechanical properties of elderly human vertebral trabecular bone
Journal of Orthopaedic Research, 2011Co-Authors: Hélène Follet, Evelyne Gineyts, Baptiste Dépalle, Yohann Bala, Françoise Munoz, Monique Arlot, Georges Boivin, Stephanie Viguetcarrin, Brigitte Burtpichat, Roland ChapurlatAbstract:Previous studies have shown that the mechanical properties of trabecular bone are determined by bone volume fraction (BV/TV) and microarchitecture. The purpose of this study was to explore other possible determinants of the mechanical properties of vertebral trabecular bone, namely Collagen Cross-Link content, microdamage, and mineralization. Trabecular bone cores were collected from human L2 vertebrae (n = 49) from recently deceased donors 54–95 years of age (21 men and 27 women). Two trabecular cores were obtained from each vertebra, one for preexisting microdamage and mineralization measurements, and one for BV/TV and quasi-static compression tests. Collagen Cross-Link content (PYD, DPD, and PEN) was measured on surrounding trabecular bone. Advancing age was associated with impaired mechanical properties, and with increased microdamage, even after adjustment by BV/TV. BV/TV was the strongest determinant of elastic modulus and ultimate strength (r2 = 0.44 and 0.55, respectively). Microdamage, mineralization parameters, and Collagen Cross-Link content were not associated with mechanical properties. These data indicate that the compressive strength of human vertebral trabecular bone is primarily determined by the amount of trabecular bone, and notably unaffected by normal variation in other factors, such as Cross-Link profile, microdamage and mineralization. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:481–488, 2011
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Association between Collagen Cross-Links and trabecular microarchitecture properties of human vertebral bone.
BONE, 2010Co-Authors: Stéphanie Viguet-carrin, Jean-paul Roux, Evelyne Gineyts, Hélène Follet, Françoise Munoz, Roland Chapurlat, Pierre Delmas, Mary BouxseinAbstract:It has been suggested that age-related deterioration in trabecular microarchitecture and changes in Collagen Cross-Link concentrations may contribute to skeletal fragility. To further explore this hypothesis, we determined the relationships among trabecular bone volume fraction (BV/TV), microarchitecture, Collagen Cross-Link content, and bone turnover in human vertebral trabecular bone. Trabecular bone specimens from L2 vertebrae were collected from 51 recently deceased donors (54-95 years of age; 20 men and 30 women). Trabecular bone volume and microarchitecture was assessed by microCT and bone formation, reflected by osteoid surface (OS/BS, %), was measured by 2D histomorphometry. Pyridinoline (PYD), deoxypyridinoline (DPD), pentosidine (PEN) and Collagen content in the cancellous bone were analysed by high-performance liquid chromatography. Associations between variables were investigated by Pearson correlations and multiple regression models, which were constructed with BV/TV and Collagen Cross-Links as explanatory variables and microarchitecture parameters as the dependent variables. RESULTS: Microarchitecture parameters were modestly to strongly correlated with BV/TV (r(2)=0.10-0.71). The amount of mature enzymatic PYD and DPD Cross-Links were not associated with the microarchitecture, either before or after adjustment for BV/TV. However, there was a positive correlation between PEN content and trabecular number (r=0.45, p=0.001) and connectivity density (r=0.40, p=0.004), and a negative correlation between PEN content and trabecular separation (r=-0.29, p=0.04). In the multiple regression models including BV/TV, age and PEN content was still significantly associated with several of the microarchitecture variables. In summary, this study suggests a link between trabecular microarchitecture and the Collagen Cross-Link profile. As PEN reflects non-enzymatic glycation of Collagen and generally increases with bone age, the association between PEN and trabecular architecture suggests that the preserved trabeculae may contain mainly old bone and have undergone little remodeling. Thus, vertebral fragility may not only be due to alterations in bone architecture but also to modification of Collagen Cross-Link patterns thereby influencing bone's mechanical behavior.
Rajarathnam E. Reddy - One of the best experts on this subject based on the ideXlab platform.
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Total Synthesis of (+)-Deoxypyrrololine: A Potential Biochemical Marker for Diagnosis of Osteoporosis.
Angewandte Chemie (International ed. in English), 1999Co-Authors: Maciej Adamczyk, Donald D. Johnson, Rajarathnam E. ReddyAbstract:The Collagen Cross-Link (+)-deoxypyrrololine (Dpl, 1), a potential biochemical marker for diagnosis of osteoporosis, has been obtained by a general and convergent total synthesis. The key synthetic features involve utilization of a L-glutamic acid derivative as a source for all three chiral centers in (+)-1, and construction of the pyrrole ring by condensation of an α-acetoxynitro compound with benzyl isocyanoacetate.
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total synthesis of deoxypyrrololine a potential biochemical marker for diagnosis of osteoporosis
Angewandte Chemie, 1999Co-Authors: Maciej Adamczyk, Donald D. Johnson, Rajarathnam E. ReddyAbstract:The Collagen Cross-Link (+)-deoxypyrrololine (Dpl, 1), a potential biochemical marker for diagnosis of osteoporosis, has been obtained by a general and convergent total synthesis. The key synthetic features involve utilization of a L-glutamic acid derivative as a source for all three chiral centers in (+)-1, and construction of the pyrrole ring by condensation of an α-acetoxynitro compound with benzyl isocyanoacetate.
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versatile synthesis of deoxypyridinoline a biochemical marker for diagnosis of osteoporosis
Tetrahedron-asymmetry, 1999Co-Authors: Maciej Adamczyk, Srinivasa Rao Akireddy, Rajarathnam E. ReddyAbstract:Abstract A versatile chiral synthesis of the bone Collagen Cross-Link, (+)-deoxypyridinoline (Dpd, 1 ) was described starting from a 3-hydroxypyridine derivative ( 2 ) via sequential introduction of three amino acid chains followed by hydrolysis. The key synthon 2 , was prepared from vitamin B 6 ( 6 ).
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VERSATILE SYNTHESIS OF (+)-DEOXYPYRIDINOLINE, A BIOCHEMICAL MARKER FOR DIAGNOSIS OF OSTEOPOROSIS
Tetrahedron: Asymmetry, 1999Co-Authors: Maciej Adamczyk, Srinivasa Rao Akireddy, Rajarathnam E. ReddyAbstract:Abstract A versatile chiral synthesis of the bone Collagen Cross-Link, (+)-deoxypyridinoline (Dpd, 1 ) was described starting from a 3-hydroxypyridine derivative ( 2 ) via sequential introduction of three amino acid chains followed by hydrolysis. The key synthon 2 , was prepared from vitamin B 6 ( 6 ).
Jan Kitajewski - One of the best experts on this subject based on the ideXlab platform.
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extracellular matrix rigidity modulates human cervical smooth muscle contractility new insights into premature cervical failure and spontaneous preterm birth
Reproductive Sciences, 2021Co-Authors: Joy Vink, Sudip Dahal, James Lohner, Conrad Sternasher, Mirella Mourad, George Davis, Zenghui Xue, Shuang Wang, Kristin M Myers, Jan KitajewskiAbstract:Spontaneous preterm birth (sPTB), a major cause of infant morbidity and mortality, must involve premature cervical softening/dilation for a preterm vaginal delivery to occur. Yet, the mechanism behind premature cervical softening/dilation in humans remains unclear. We previously reported the non-pregnant human cervix contains considerably more cervical smooth muscle cells (CSMC) than historically appreciated and the CSMC organization resembles a sphincter. We hypothesize that premature cervical dilation leading to sPTB may be due to (1) an inherent CSMC contractility defect resulting in sphincter failure and/or (2) altered cervical extracellular matrix (ECM) rigidity which influences CSMC contractility. To test these hypotheses, we utilized immunohistochemistry to confirm this CSMC phenotype persists in the human pregnant cervix and then assessed in vitro arrays of contractility (F:G actin ratios, PDMS pillar arrays) using primary CSMC from pregnant women with and without premature cervical failure (PCF). We show that CSMC from pregnant women with PCF do not have an inherent CSMC contractility defect but that CSMC exhibit decreased contractility when exposed to soft ECM. Given this finding, we used UPLC-ESI-MS/MS to evaluate Collagen Cross-Link profiles in the cervical tissue from non-pregnant women with and without PCF and found that women with PCF have decreased Collagen Cross-Link maturity ratios, which correlates to softer cervical tissue. These findings suggest having soft cervical ECM may lead to decreased CSMC contractile tone and a predisposition to sphincter laxity that contributes to sPTB. Further studies are needed to explore the interaction between cervical ECM properties and CSMC cellular behavior when investigating the pathophysiology of sPTB.
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Extracellular Matrix Rigidity Modulates Human Cervical Smooth Muscle Contractility—New Insights into Premature Cervical Failure and Spontaneous Preterm Birth
Reproductive Sciences, 2020Co-Authors: Joy Vink, Sudip Dahal, James Lohner, Mirella Mourad, George Davis, Shuang Wang, Victoria Yu, Conrad Stern-asher, Kristin Myers, Jan KitajewskiAbstract:Spontaneous preterm birth (sPTB), a major cause of infant morbidity and mortality, must involve premature cervical softening/dilation for a preterm vaginal delivery to occur. Yet, the mechanism behind premature cervical softening/dilation in humans remains unclear. We previously reported the non-pregnant human cervix contains considerably more cervical smooth muscle cells (CSMC) than historically appreciated and the CSMC organization resembles a sphincter. We hypothesize that premature cervical dilation leading to sPTB may be due to (1) an inherent CSMC contractility defect resulting in sphincter failure and/or (2) altered cervical extracellular matrix (ECM) rigidity which influences CSMC contractility. To test these hypotheses, we utilized immunohistochemistry to confirm this CSMC phenotype persists in the human pregnant cervix and then assessed in vitro arrays of contractility (F:G actin ratios, PDMS pillar arrays) using primary CSMC from pregnant women with and without premature cervical failure (PCF). We show that CSMC from pregnant women with PCF do not have an inherent CSMC contractility defect but that CSMC exhibit decreased contractility when exposed to soft ECM. Given this finding, we used UPLC-ESI-MS/MS to evaluate Collagen Cross-Link profiles in the cervical tissue from non-pregnant women with and without PCF and found that women with PCF have decreased Collagen Cross-Link maturity ratios, which correlates to softer cervical tissue. These findings suggest having soft cervical ECM may lead to decreased CSMC contractile tone and a predisposition to sphincter laxity that contributes to sPTB. Further studies are needed to explore the interaction between cervical ECM properties and CSMC cellular behavior when investigating the pathophysiology of sPTB.
Mitsuo Yamauchi - One of the best experts on this subject based on the ideXlab platform.
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type iii Collagen is a key regulator of the Collagen fibrillar structure and biomechanics of articular cartilage and meniscus
Matrix Biology, 2020Co-Authors: Chao Wang, Masahiko Terajima, Becky K Brisson, Kevther Hoxha, Biao Han, Abby M Goldberg, Sherry X Liu, Michele Marcolongo, Motomi Enomotoiwamoto, Mitsuo YamauchiAbstract:Despite the fact that type III Collagen is the second most abundant Collagen type in the body, its contribution to the physiologic maintenance and repair of skeletal tissues remains poorly understood. This study queried the role of type III Collagen in the structure and biomechanical functions of two structurally distinctive tissues in the knee joint, type II Collagen-rich articular cartilage and type I Collagen-dominated meniscus. Integrating outcomes from atomic force microscopy-based nanomechanical tests, Collagen fibril nanostructural analysis, Collagen Cross-Link analysis and histology, we elucidated the impact of type III Collagen haplodeficiency on the morphology, nanostructure and biomechanical properties of articular cartilage and meniscus in Col3a1+/- mice. Reduction of type III Collagen leads to increased heterogeneity and mean thickness of Collagen fibril diameter, as well as reduced modulus in both tissues, and these effects became more pronounced with skeletal maturation. These data suggest a crucial role of type III Collagen in mediating fibril assembly and biomechanical functions of both articular cartilage and meniscus during post-natal growth. In articular cartilage, type III Collagen has a marked contribution to the micromechanics of the pericellular matrix, indicating a potential role in mediating the early stage of type II Collagen fibrillogenesis and chondrocyte mechanotransduction. In both tissues, reduction of type III Collagen leads to decrease in tissue modulus despite the increase in Collagen Cross-Linking. This suggests that the disruption of matrix structure due to type III Collagen deficiency outweighs the stiffening of Collagen fibrils by increased Cross-Linking, leading to a net negative impact on tissue modulus. Collectively, this study is the first to highlight the crucial structural role of type III Collagen in both articular cartilage and meniscus extracellular matrices. We expect these results to expand our understanding of type III Collagen across various tissue types, and to uncover critical molecular components of the microniche for regenerative strategies targeting articular cartilage and meniscus repair.
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The fibrotic tumor stroma
The Journal of clinical investigation, 2018Co-Authors: Mitsuo Yamauchi, Thomas H Barker, Don L. Gibbons, Jonathan M. KurieAbstract:Intratumoral fibrosis results from the deposition of a Cross-Linked Collagen matrix by cancer-associated fibroblasts (CAFs). This type of fibrosis has been shown to exert mechanical forces and create a biochemical milieu that, together, shape intratumoral immunity and influence tumor cell metastatic behavior. In this Review, we present recent evidence that CAFs and tumor cells are regulated by provisional matrix molecules, that metastasis results from a change in the type of stromal Collagen Cross-Link, and that fibrosis and inflammation perpetuate each other through proteolytic and chemotactic mediators released into the tumor stroma. We also discuss aspects of the emerging biology that have potential therapeutic value.
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FKBP65-dependent peptidyl-prolyl isomerase activity potentiates the lysyl hydroxylase 2-driven Collagen Cross-Link switch
Scientific Reports, 2017Co-Authors: Yulong Chen, Jiang Yu, Masahiko Terajima, Priyam Banerjee, Mitsuo Yamauchi, Jonathan M. KurieAbstract:Bruck Syndrome is a connective tissue disease associated with inactivating mutations in lysyl hydroxylase 2 (LH2/PLOD2) or FK506 binding protein 65 (FKBP65/FKBP10). However, the functional relationship between LH2 and FKBP65 remains unclear. Here, we postulated that peptidyl prolyl isomerase (PPIase) activity of FKBP65 positively modulates LH2 enzymatic activity and is critical for the formation of hydroxylysine-aldehyde derived intermolecular Collagen Cross-Links (HLCCs). To test this hypothesis, we analyzed Collagen Cross-Links in Fkbp10-null and –wild-type murine embryonic fibroblasts. Although LH2 protein levels did not change, FKBP65 deficiency significantly diminished HLCCs and increased the non-hydroxylated lysine-aldehyde–derived Collagen Cross-Links (LCCs), a pattern consistent with loss of LH2 enzymatic activity. The HLCC-to-LCC ratio was rescued in FKBP65-deficient murine embryonic fibroblasts by reconstitution with wild-type but not mutant FKBP65 that lacks intact PPIase domains. Findings from co-immunoprecipitation, protein-fragment complementation, and co-immunofluorescence assays showed that LH2 and FKBP65 are part of a common protein complex. We conclude that FKBP65 regulates LH2-mediated Collagen Cross-Linking. Because LH2 promotes fibrosis and cancer metastasis, our findings suggest that pharmacologic strategies to target FKBP65 and LH2 may have complementary therapeutic activities.
Hélène Follet - One of the best experts on this subject based on the ideXlab platform.
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Relationships between human cortical bone toughness and Collagen Cross-Links on paired anatomical locations
BONE, 2018Co-Authors: Rémy Gauthier, Evelyne Gineyts, Hélène Follet, Max Langer, Frédéric Rongieras, Françoise Peyrin, David MittonAbstract:Human cortical bone fracture processes depend on the internal porosity network down to the lacunar length scale. Recent results show that at the Collagen scale, the maturation of Collagen Cross-Links may have a negative influence on bone mechanical behavior. While the effect of pentosidine on human cortical bone toughness has been studied, the influence of mature and immature enzymatic Cross-Links has only been studied in relation to strength and work of fracture. Moreover, these relationships have not been studied on different paired anatomical locations. Thus, the aim of the current study was to assess the relationships between both enzymatic and non-enzymatic Collagen Cross-Links and human cortical bone toughness, on four human paired anatomical locations. Single Edge Notched Bending toughness tests were performed for two loading conditions: a quasi-static standard condition, and a condition representative of a fall. These tests were done with 32 paired femoral diaphyses, femoral necks and radial diaphyses (18 women, age 81±12 y.o.; 14 men, age 79±8 y.o.). Collagen enzymatic and non-enzymatic crosslinks were measured on the same bones. Maturation of Collagen was defined as the ratio between immature and mature Cross-Links (CX). The results show that there was a significant correlation between Collagen Cross-Link maturation and bone toughness when gathering femoral and radial diaphyses, but not when considering each anatomical location individually. These results show that the influence of Collagen enzymatic and non-enzymatic Cross-Links is minor when considering human cortical bone crack propagation mechanisms.
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Determinants of microdamage in elderly human vertebral trabecular bone.
PloS one, 2013Co-Authors: Hélène Follet, Evelyne Gineyts, Pierre D Delmas, Brigitte Burt-pichat, Stéphanie Viguet-carrin, Yohann Bala, Georges Boivin, Delphine Farlay, Julien Wegrzyn, Roland ChapurlatAbstract:Previous studies have shown that microdamage accumulates in bone as a result of physiological loading and occurs naturally in human trabecular bone. The purpose of this study was to determine the factors associated with pre-existing microdamage in human vertebral trabecular bone, namely age, architecture, hardness, mineral and organic matrix. Trabecular bone cores were collected from human L2 vertebrae (n = 53) from donors 54-95 years of age (22 men and 30 women, 1 unknown) and previous cited parameters were evaluated. Collagen Cross-Link content (PYD, DPD, PEN and % of Collagen) was measured on surrounding trabecular bone. We found that determinants of microdamage were mostly the age of donors, architecture, mineral characteristics and mature enzymatic Cross-Links. Moreover, linear microcracks were mostly associated with the bone matrix characteristics whereas diffuse damage was associated with architecture. We conclude that linear and diffuse types of microdamage seemed to have different determinants, with age being critical for both types.
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Effects of preexisting microdamage, Collagen Cross-Links, degree of mineralization, age, and architecture on compressive mechanical properties of elderly human vertebral trabecular bone.
Journal of Orthopaedic Research, 2011Co-Authors: Hélène Follet, Evelyne Gineyts, Brigitte Burt-pichat, Stéphanie Viguet-carrin, Baptiste Dépalle, Yohann Bala, Françoise Munoz, Monique Arlot, Georges Boivin, Roland ChapurlatAbstract:Previous studies have shown that the mechanical properties of trabecular bone are determined by bone volume fraction (BV/TV) and microarchitecture. The purpose of this study was to explore other possible determinants of the mechanical properties of vertebral trabecular bone, namely Collagen Cross-Link content, microdamage, and mineralization. Trabecular bone cores were collected from human L2 vertebrae (n = 49) from recently deceased donors 54-95 years of age (21 men and 27 women). Two trabecular cores were obtained from each vertebra, one for preexisting microdamage and mineralization measurements, and one for BV/TV and quasi-static compression tests. Collagen Cross-Link content (PYD, DPD, and PEN) was measured on surrounding trabecular bone. Advancing age was associated with impaired mechanical properties, and with increased microdamage, even after adjustment by BV/TV. BV/TV was the strongest determinant of elastic modulus and ultimate strength (r² = 0.44 and 0.55, respectively). Microdamage, mineralization parameters, and Collagen Cross-Link content were not associated with mechanical properties. These data indicate that the compressive strength of human vertebral trabecular bone is primarily determined by the amount of trabecular bone, and notably unaffected by normal variation in other factors, such as Cross-Link profile, microdamage and mineralization.
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effects of preexisting microdamage Collagen cross links degree of mineralization age and architecture on compressive mechanical properties of elderly human vertebral trabecular bone
Journal of Orthopaedic Research, 2011Co-Authors: Hélène Follet, Evelyne Gineyts, Baptiste Dépalle, Yohann Bala, Françoise Munoz, Monique Arlot, Georges Boivin, Stephanie Viguetcarrin, Brigitte Burtpichat, Roland ChapurlatAbstract:Previous studies have shown that the mechanical properties of trabecular bone are determined by bone volume fraction (BV/TV) and microarchitecture. The purpose of this study was to explore other possible determinants of the mechanical properties of vertebral trabecular bone, namely Collagen Cross-Link content, microdamage, and mineralization. Trabecular bone cores were collected from human L2 vertebrae (n = 49) from recently deceased donors 54–95 years of age (21 men and 27 women). Two trabecular cores were obtained from each vertebra, one for preexisting microdamage and mineralization measurements, and one for BV/TV and quasi-static compression tests. Collagen Cross-Link content (PYD, DPD, and PEN) was measured on surrounding trabecular bone. Advancing age was associated with impaired mechanical properties, and with increased microdamage, even after adjustment by BV/TV. BV/TV was the strongest determinant of elastic modulus and ultimate strength (r2 = 0.44 and 0.55, respectively). Microdamage, mineralization parameters, and Collagen Cross-Link content were not associated with mechanical properties. These data indicate that the compressive strength of human vertebral trabecular bone is primarily determined by the amount of trabecular bone, and notably unaffected by normal variation in other factors, such as Cross-Link profile, microdamage and mineralization. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:481–488, 2011
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Association between Collagen Cross-Links and trabecular microarchitecture properties of human vertebral bone.
BONE, 2010Co-Authors: Stéphanie Viguet-carrin, Jean-paul Roux, Evelyne Gineyts, Hélène Follet, Françoise Munoz, Roland Chapurlat, Pierre Delmas, Mary BouxseinAbstract:It has been suggested that age-related deterioration in trabecular microarchitecture and changes in Collagen Cross-Link concentrations may contribute to skeletal fragility. To further explore this hypothesis, we determined the relationships among trabecular bone volume fraction (BV/TV), microarchitecture, Collagen Cross-Link content, and bone turnover in human vertebral trabecular bone. Trabecular bone specimens from L2 vertebrae were collected from 51 recently deceased donors (54-95 years of age; 20 men and 30 women). Trabecular bone volume and microarchitecture was assessed by microCT and bone formation, reflected by osteoid surface (OS/BS, %), was measured by 2D histomorphometry. Pyridinoline (PYD), deoxypyridinoline (DPD), pentosidine (PEN) and Collagen content in the cancellous bone were analysed by high-performance liquid chromatography. Associations between variables were investigated by Pearson correlations and multiple regression models, which were constructed with BV/TV and Collagen Cross-Links as explanatory variables and microarchitecture parameters as the dependent variables. RESULTS: Microarchitecture parameters were modestly to strongly correlated with BV/TV (r(2)=0.10-0.71). The amount of mature enzymatic PYD and DPD Cross-Links were not associated with the microarchitecture, either before or after adjustment for BV/TV. However, there was a positive correlation between PEN content and trabecular number (r=0.45, p=0.001) and connectivity density (r=0.40, p=0.004), and a negative correlation between PEN content and trabecular separation (r=-0.29, p=0.04). In the multiple regression models including BV/TV, age and PEN content was still significantly associated with several of the microarchitecture variables. In summary, this study suggests a link between trabecular microarchitecture and the Collagen Cross-Link profile. As PEN reflects non-enzymatic glycation of Collagen and generally increases with bone age, the association between PEN and trabecular architecture suggests that the preserved trabeculae may contain mainly old bone and have undergone little remodeling. Thus, vertebral fragility may not only be due to alterations in bone architecture but also to modification of Collagen Cross-Link patterns thereby influencing bone's mechanical behavior.