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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.<\/jats:p>","DOI":"10.1093\/hmg\/ddaa006","type":"journal-article","created":{"date-parts":[[2020,1,10]],"date-time":"2020-01-10T12:13:22Z","timestamp":1578658402000},"page":"803-816","source":"Crossref","is-referenced-by-count":17,"title":["Enzyme replacement therapy in mice lacking arylsulfatase B targets bone-remodeling cells, but not chondrocytes"],"prefix":"10.1093","volume":"29","author":[{"given":"Gretl","family":"Hendrickx","sequence":"first","affiliation":[{"name":"Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatyana","family":"Danyukova","sequence":"first","affiliation":[{"name":"Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, 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20246 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johannes","family":"Keller","sequence":"first","affiliation":[{"name":"Center for Musculoskeletal Surgery, Charit\u00e9 University Medicine, 10117 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00f6rg","family":"Schr\u00f6der","sequence":"first","affiliation":[{"name":"Center for Musculoskeletal Surgery, Charit\u00e9 University Medicine, 10117 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine","family":"Meyer-Schwesinger","sequence":"first","affiliation":[{"name":"Institute of Cellular and Integrative Physiology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole","family":"Muschol","sequence":"first","affiliation":[{"name":"International Center for Lysosomal Diseases, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Paganini","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine, University of Pavia, 27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Rossi","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine, University of Pavia, 27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Amling","sequence":"first","affiliation":[{"name":"Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Pohl","sequence":"first","affiliation":[{"name":"Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thorsten","family":"Schinke","sequence":"first","affiliation":[{"name":"Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,1,15]]},"reference":[{"key":"2020033008550252900_ref1","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.bone.2015.04.035","article-title":"Bone development","volume":"80","author":"Berendsen","year":"2015","journal-title":"Bone"},{"key":"2020033008550252900_ref2","doi-asserted-by":"crossref","first-page":"e23248","DOI":"10.1002\/dvg.23248","article-title":"A tale of two cities: the genetic mechanisms governing calvarial bone 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