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Enzyme replacement therapy in mice lacking arylsulfatase B targets bone remodeling cells, but not chondrocytes

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Enzyme replacement therapy in mice lacking arylsulfatase B targets bone remodeling cells, but not chondrocytes. / Hendrickx, Gretl; Danyukova, Tatyana; Baranowsky, Anke; Rolvien, Tim; Angermann, Alexandra; Schweizer, Michaela; Keller, Johannes; Schröder, Jörg; Meyer-Schwesinger, Catherine; Muschol, Nicole; Paganini, Chiara; Rossi, Antonio; Amling, Michael; Pohl, Sandra; Schinke, Thorsten.

In: HUM MOL GENET, Vol. 29, No. 5, 27.03.2020, p. 803-816.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Hendrickx, G, Danyukova, T, Baranowsky, A, Rolvien, T, Angermann, A, Schweizer, M, Keller, J, Schröder, J, Meyer-Schwesinger, C, Muschol, N, Paganini, C, Rossi, A, Amling, M, Pohl, S & Schinke, T 2020, 'Enzyme replacement therapy in mice lacking arylsulfatase B targets bone remodeling cells, but not chondrocytes', HUM MOL GENET, vol. 29, no. 5, pp. 803-816. https://doi.org/10.1093/hmg/ddaa006

APA

Hendrickx, G., Danyukova, T., Baranowsky, A., Rolvien, T., Angermann, A., Schweizer, M., Keller, J., Schröder, J., Meyer-Schwesinger, C., Muschol, N., Paganini, C., Rossi, A., Amling, M., Pohl, S., & Schinke, T. (2020). Enzyme replacement therapy in mice lacking arylsulfatase B targets bone remodeling cells, but not chondrocytes. HUM MOL GENET, 29(5), 803-816. https://doi.org/10.1093/hmg/ddaa006

Vancouver

Hendrickx G, Danyukova T, Baranowsky A, Rolvien T, Angermann A, Schweizer M et al. Enzyme replacement therapy in mice lacking arylsulfatase B targets bone remodeling cells, but not chondrocytes. HUM MOL GENET. 2020 Mar 27;29(5):803-816. https://doi.org/10.1093/hmg/ddaa006

Bibtex

@article{e2382881be9b4a8aadc8ba8eede84b8e,
title = "Enzyme replacement therapy in mice lacking arylsulfatase B targets bone remodeling cells, but not chondrocytes",
abstract = "Mucopolysaccharidosis type VI (MPS-VI), caused by mutational inactivation of the glycosaminoglycan-degrading enzyme arylsulfatase B (Arsb), is a lysosomal storage disorder primarily affecting the skeleton. We have previously reported that Arsb-deficient mice display high trabecular bone mass and impaired skeletal growth. In the present study, we treated them by weekly injection of recombinant human ARSB (rhARSB) to analyze the impact of enzyme replacement therapy (ERT) on skeletal growth and bone remodeling. We found that all bone remodeling abnormalities of Arsb-deficient mice were prevented by ERT, whereas chondrocyte defects were not. Likewise, histologic analysis of the surgically removed femoral head from an ERT-treated MPS-VI patient revealed that only chondrocytes were pathologically affected. Remarkably, a side-by-side comparison with other cell types demonstrated that chondrocytes have substantially reduced capacity to endocytose rhARSB, together with low expression of the mannose receptor. We finally took advantage of Arsb-deficient mice to establish quantification of chondroitin sulfation for treatment monitoring. Our data demonstrate that bone remodeling cell types are accessible to systemically delivered rhARSB, whereas the uptake into chondrocytes is inefficient.",
author = "Gretl Hendrickx and Tatyana Danyukova and Anke Baranowsky and Tim Rolvien and Alexandra Angermann and Michaela Schweizer and Johannes Keller and J{\"o}rg Schr{\"o}der and Catherine Meyer-Schwesinger and Nicole Muschol and Chiara Paganini and Antonio Rossi and Michael Amling and Sandra Pohl and Thorsten Schinke",
note = "{\textcopyright} The Author(s) 2020. Published by Oxford University Press.",
year = "2020",
month = mar,
day = "27",
doi = "10.1093/hmg/ddaa006",
language = "English",
volume = "29",
pages = "803--816",
journal = "HUM MOL GENET",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "5",

}

RIS

TY - JOUR

T1 - Enzyme replacement therapy in mice lacking arylsulfatase B targets bone remodeling cells, but not chondrocytes

AU - Hendrickx, Gretl

AU - Danyukova, Tatyana

AU - Baranowsky, Anke

AU - Rolvien, Tim

AU - Angermann, Alexandra

AU - Schweizer, Michaela

AU - Keller, Johannes

AU - Schröder, Jörg

AU - Meyer-Schwesinger, Catherine

AU - Muschol, Nicole

AU - Paganini, Chiara

AU - Rossi, Antonio

AU - Amling, Michael

AU - Pohl, Sandra

AU - Schinke, Thorsten

N1 - © The Author(s) 2020. Published by Oxford University Press.

PY - 2020/3/27

Y1 - 2020/3/27

N2 - Mucopolysaccharidosis type VI (MPS-VI), caused by mutational inactivation of the glycosaminoglycan-degrading enzyme arylsulfatase B (Arsb), is a lysosomal storage disorder primarily affecting the skeleton. We have previously reported that Arsb-deficient mice display high trabecular bone mass and impaired skeletal growth. In the present study, we treated them by weekly injection of recombinant human ARSB (rhARSB) to analyze the impact of enzyme replacement therapy (ERT) on skeletal growth and bone remodeling. We found that all bone remodeling abnormalities of Arsb-deficient mice were prevented by ERT, whereas chondrocyte defects were not. Likewise, histologic analysis of the surgically removed femoral head from an ERT-treated MPS-VI patient revealed that only chondrocytes were pathologically affected. Remarkably, a side-by-side comparison with other cell types demonstrated that chondrocytes have substantially reduced capacity to endocytose rhARSB, together with low expression of the mannose receptor. We finally took advantage of Arsb-deficient mice to establish quantification of chondroitin sulfation for treatment monitoring. Our data demonstrate that bone remodeling cell types are accessible to systemically delivered rhARSB, whereas the uptake into chondrocytes is inefficient.

AB - Mucopolysaccharidosis type VI (MPS-VI), caused by mutational inactivation of the glycosaminoglycan-degrading enzyme arylsulfatase B (Arsb), is a lysosomal storage disorder primarily affecting the skeleton. We have previously reported that Arsb-deficient mice display high trabecular bone mass and impaired skeletal growth. In the present study, we treated them by weekly injection of recombinant human ARSB (rhARSB) to analyze the impact of enzyme replacement therapy (ERT) on skeletal growth and bone remodeling. We found that all bone remodeling abnormalities of Arsb-deficient mice were prevented by ERT, whereas chondrocyte defects were not. Likewise, histologic analysis of the surgically removed femoral head from an ERT-treated MPS-VI patient revealed that only chondrocytes were pathologically affected. Remarkably, a side-by-side comparison with other cell types demonstrated that chondrocytes have substantially reduced capacity to endocytose rhARSB, together with low expression of the mannose receptor. We finally took advantage of Arsb-deficient mice to establish quantification of chondroitin sulfation for treatment monitoring. Our data demonstrate that bone remodeling cell types are accessible to systemically delivered rhARSB, whereas the uptake into chondrocytes is inefficient.

U2 - 10.1093/hmg/ddaa006

DO - 10.1093/hmg/ddaa006

M3 - SCORING: Journal article

C2 - 31943020

VL - 29

SP - 803

EP - 816

JO - HUM MOL GENET

JF - HUM MOL GENET

SN - 0964-6906

IS - 5

ER -