Growth Parameters in the Epiphyseal Cartilage of Brachymorphic (bm/bm) Mice

Vanky, Peter; Brockstedt, Ulrika; Nurminen, M.; Wikström, B.; Hjerpe, Anders

doi:10.1007/s002230010073

Cited by 9 publications

(18 citation statements)

References 30 publications

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“…To gain new insight in the pathogenesis of different forms of human chondrodysplasias, different mouse strains bearing natural or artificially induced mutations have been studied, including brachymorphic mice with natural alterations in sulphation pathway and transgenic mice carrying mutations in ECM protein genes [19][20][21]. Interestingly, our data concerning cell proliferation in dtdts mutant animals are consistent with those observed in brachymorphic mice [19].…”

Section: Discussionsupporting

confidence: 71%

“…We have studied the histogenesis of EGP in this model using different microscopical techniques, as it done previously to study other forms of chondrodysplasia in the animal [19][20][21]. In particular, using ultrastructural and histochemical methods, it was possible to reveal several differences in the growth plate of dtdst knock-in mouse compared to normal mouse; such differences included reduction in chondrocyte growth, modifications in chondrocyte differentiation, and alterations in ECM organization and composition.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, selective isolation of the plate from the surrounding tissues (including bone, bone marrow, blood vessels, and dense connective tissue) cannot be obtained precisely, and reliable biochemical analyses cannot be performed ex vivo. In line with other investigations on the growth plate [1,4,19,20,21], we decided to investigate the histogenesis of EGP in dtdst-mutant mouse using microscopical methods, including histochemical and electron microscopical analyses.…”

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confidence: 99%

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Dysplastic Histogenesis of Cartilage Growth Plate by Alteration of Sulphation Pathway: A Transgenic Model

Cornaglia

Casasco

et al. 2009

Connective Tissue Research

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Mutations in the diastrophic dysplasia sulphate transporter (dtdst) gene causes different forms of chondrodysplasia in the human. The generation of a knock-in mouse strain with a mutation in dtdst gene provides the basis to study developmental dynamics in the epiphyseal growth plate and long bone growth after impairment of the sulphate pathway. Our microscopical and histochemical data demonstrate that dtdst gene impairment deeply affects tissue organization, matrix structure, and cell differentiation in the epiphyseal growth plate. In mutant animals, the height of the growth plate was significantly reduced, according to a concomitant decrease in cell density and proliferation. Although the pathway of chondrocyte differentiation seemed complete, alteration in cell morphology compared to normal counterparts was detected. In the extracellular matrix, it we observed a dramatic decrease in sulphated proteoglycans, alterations in the organization of type II and type X collagen fibers, and premature onset of mineralization. These data confirm the crucial role of sulphate pathway in proteoglycan biochemistry and suggest that a disarrangement of the extracellular matrix may be responsible for the development of dtdts cartilage dysplasia. Moreover, we corroborated the concept that proteoglycans not only are structural components of the cartilage architecture, but also play a dynamic role in the regulation of chondrocyte growth and differentiation.

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Section: Discussionsupporting

confidence: 71%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Dysplastic Histogenesis of Cartilage Growth Plate by Alteration of Sulphation Pathway: A Transgenic Model

Cornaglia

Casasco

et al. 2009

Connective Tissue Research

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“…Although experimentally observed cell height reductions under these conditions exceed our predictions, Gakunga et al (2000) and Vanky et al (2000) also show reduced hypertrophy when hyaluronan is absent (∼20%), reduced (∼18%), or not well retained in the tissue (∼10%).…”

Section: Resultscontrasting

confidence: 62%

“…After corroborating model predictions with the literature, we alter selective parameters and compare predictions with effects that are known to occur experimentally. These include extended simulations to accommodate more extreme terminal cell sizes (Hunziker 1994), application of axial tension or compression to corroborate the Hueter-Volkmann principle, which says that bone growth in epiphyseal plates is load-dependently reduced by compression and enhanced by tension and is predominantly the results of changes in the rate of hypertrophy and the ultimate size of hypertrophic cells (Stokes 2002;Stokes et al 2007Stokes et al , 2005, and simulations of hypertrophy in case of partially or fully compromised proteoglycan expression (Vanky et al 2000). Finally, we explore how mechanical conditions may be involved in the aforementioned S1Pcko knock-out mouse model in which cells do not hypertrophy (Patra et al 2006a,b).…”

Section: Introductionmentioning

confidence: 99%

Mechanics of chondrocyte hypertrophy

Donkelaar

Wilson

2011

Biomech Model Mechanobiol

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Chondrocyte hypertrophy is a characteristic of osteoarthritis and dominates bone growth. Intra-and extracellular changes that are known to be induced by metabolically active hypertrophic chondrocytes are known to contribute to hypertrophy. However, it is unknown to which extent these mechanical conditions together can be held responsible for the total magnitude of hypertrophy. The present paper aims to provide a quantitative, mechanically sound answer to that question. To address this aim requires a quantitative tool that captures the mechanical effects of collagen and proteoglycans, allows temporal changes in tissue composition, and can compute cell and tissue deformations. These requirements are met in our numerical model that is validated for articular cartilage mechanics, which we apply to quantitatively explain a range of experimental observations related to hypertrophy. After validating the numerical approach for studying hypertrophy, the model is applied to evaluate the direct mechanical effects of axial tension and compression on hypertrophy (Hueter-Volkmann principle) and to explore why hypertrophy is reduced in case of partially or fully compromised proteoglycan expression. Finally, a mechanical explanation is provided for the observation that chondrocytes do not hypertrophy when enzymatical collagen degradation is prohibited (S1Pcko knock-out mouse model). This paper shows that matrix turnover by metabolically active chondrocytes, together with externally applied mechanical conditions, can explain quantitatively the volumetric change of chondrocytes during hypertrophy. It provides a mechanistic explanation for the observation that collagen degradation results in chondrocyte hypertrophy, both under physiological and pathological conditions.

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In Vivo Analysis of Arg-Gly-Asp Sequence/Integrin α5β1-Mediated Signal Involvement in Embryonic Enchondral Ossification by Exo Utero Development System

Inoue

Hashimoto

Matsumoto

et al. 2013

Journal of Bone and Mineral Research

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Enchondral ossification is a fundamental mechanism for longitudinal bone growth during vertebrate development. In vitro studies suggested that functional blockade with RGD peptides or with an antibody that interferes with integrin a5b1-ligand interactions inhibited pre-hypertrophic chondrocyte differentiation. The purpose of this study is to elucidate in vivo the roles of the integrin a5b1-mediated signal through the Arg-Gly-Asp (RGD) sequence in the cell-extracellular matrix (ECM) interaction in embryonic enchondral ossification by an exo utero development system. We injected Arg-Gly-Asp-Ser (RGDS) peptides and anti-integrin a5b1 antibody (a5b1 ab) in the upper limbs of mouse embryos at embryonic day (E) 15.5 (RGDS-injected limbs, a5b1 ab-injected limbs), and compared the effects on enchondral ossification with those found in the control limbs (Arg-Gly-Glu-Ser peptide-, mouse IgG-, or vehicle-injected, and no surgery) at E16.5. In the RGDS-injected limbs, the humeri were shorter and there were fewer BrdU-positive cells than in the control limbs. The ratios of cartilage length and area to those of the humerus were higher in the RGDS-injected limbs. The ratios of type X collagen to type 2 collagen mRNA and protein (Coll X/Coll 2) were significantly lower in the RGDS-injected limbs. In those limbs, TUNEL-positive cells were hardly observed, and the ratios of fractin to the Coll X/Coll 2 ratio were lower than in the control limbs. Furthermore, the a5b1 ab-injected limbs showed results similar to those of RGDS-injected limbs. The present in vivo study by exo utero development system showed that RGDS and a5b1 ab injection decreased chondrocyte proliferation, differentiation, and apoptosis in enchondral ossification, and suggested that the integrin a5b1-mediated ECM signal through the RGD sequence is involved in embryonic enchondral ossification.

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Growth Parameters in the Epiphyseal Cartilage of Brachymorphic (bm/bm) Mice

Cited by 9 publications

References 30 publications

Dysplastic Histogenesis of Cartilage Growth Plate by Alteration of Sulphation Pathway: A Transgenic Model

Dysplastic Histogenesis of Cartilage Growth Plate by Alteration of Sulphation Pathway: A Transgenic Model

Mechanics of chondrocyte hypertrophy

In Vivo Analysis of Arg-Gly-Asp Sequence/Integrin α5β1-Mediated Signal Involvement in Embryonic Enchondral Ossification by Exo Utero Development System

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